Dermatology, Plastic and Reconstructive Surgery, Sbobinature di Dermatologia

Scarica Dermatology, Plastic and Reconstructive Surgery e più Sbobinature in PDF di Dermatologia solo su Docsity! DERMATOLOGY, PLASTIC AND RECONSTRUCTIVE SURGERY March 2nd 2021 [Prof. S. Iurassich] Lesion types and definition ● Primitive → arise as such. Include macula (aerenchyma), papule (pimple), nodule, vesicle, bulla (blister/bubble) and wheal (urticaria). ● Primitive secondary → arise as such or they evolve from primitive. Include pustules, scale, sclerosis, atrophy. ● Secondary → evolve from primitive. Include crust, rosion, exocration, fissure, ulcer, sore, scar. Types of skin lesions ● Start or end: ○ macula (spot). ○ patch (confluence of spots). ● Solid: ○ papule (pimple). ○ plaque (confluence of papules). ○ wheal. ○ nodule (nodulus, small knot). ● Humid: ○ vesicle. ○ bulla (<0,5 cm<). ○ pustule. ● Others: ○ crust. ○ scale and desquamation (scaling). ○ ulcer (ulcus, sore). ○ erossion. ○ fissure. Vesicles/bulles → a vesicle (less than 0,5 cm) or a bulla (more than 0,5 cm) is a circumscribed elevated lesion containing fluid. Often the walls are so thin that they are translucent, and the serum, lymph fluid, blood or extracellular fluid within them can be seen. 1 Vesicle/bulla formation results from intercellular edema (spongiosis) in delayed-hypersensitivity reaction of the epidermis (contact eczematous dermatitis) and in dyshidrotic eczema. 2. Acantholysis → detachment of the demosome by antibody/acid and then edema formation. Acantholysis (in pemphigus) refers to disruption of the intercellular connections between keratinocytes of the epidermis, through immunologic or chemically mediated lysis of intercellular cement substance, resulting in a secondary disruption of desmosomes (result of disruption of desmosomal attachments). + subsequent disruption of intercellular junctions which leads to formation of intraepidermal vesicles. 4 Cadherins (calcium-dependent adhesion) are a class of type-1 transmembrane proteins which play an important role in cell adhesion, forming adherens junctions to 5 bind cells within tissues together. → desmogleins (DSG) are a family of cadherins consisting of proteins DSG1, DSG2, DSG3 and DSG4 (role in the formation of desmosomes -- “glue” between cells -- that join cells to one another = attachment points.). In pemphigus, autoantibodies form against desmogleins attacking principally DSG1 (skin) and DSG3 (skin and mucous membranes). When this occurs, the cells become separated from each other and the epidermis becomes “unglued” = acantholysis. Autoantibodies against DSG are directed against a particular region of DSGs. The desmogleins are not the cause of the autoantibodies, these are produced against other antigens (virus, bacteria) and they become autoreactive after mutations that occur during antibody maturation. These anti-DSG antibodies are of the IgG isotype and they are present at the site of the lesion and in serum. Acantholysis occurs: A) at the level of the granular layer (high or subcorneal acantholysis) for the prevalence of anti-DSG1. → typical of pemphigus foliaceus. B) at the level of the basal layer (low or suprabasal acantholysis) for the prevalence of anti-DSG3. → typical of pemphigus vulgaris. Pemphigus vulgaris → positive Nikolsky’s sign and is a characteristic finding in pemphigus. Can be elicited in thermal burns and staphylococcal scalded skin syndrome. Antibody goes against DSG1 and DSG3. → the cell separates (detachment by acantholysis) → causes blisters (bulla). The bullae are located intraepidermally, which accounts for their fragility. The blister’s roof is easily extended into the surrounding non-blister skin by pressing the perilesional skin or pulling the edge of the roof of the bullae. Older patients with multiple single bullae require a biopsy and immunofluorescence for diagnosis of pemphigus or pemphigoid. Dermo-epidermal cleavage (bullous pemphigoid) → the IgG antibodies (rarely also IgM) are directed against the junctional zone (circulating antibasement membrane IgG antibodies). IgG activates complement resulting in leukocyte chemotaxis and release of proteolytic enzymes. This process causes detachment between dermis and epidermis at the level of the upper portion of the basement membrane (lamina lucida). Antibasement membrane IgG antibodies recognize two self-antigens of the basal cell: BPAG1 and BPAG2. BPAG1 = cytoplasmic protein (plachine family) and is located at the level of emidesmosomical plaque. BPAG2 = transmembrane protein with extracellular collagen (type XVII) that forms the immunodominant epitope. 6 ● Allergic contact dermatitis → persistent or relapsing dermatitis, particularly if the material causing the allergic reaction is not identified (causes could be rubber, hair dye, perfume, preservatives, nickel - the responsible agent may be identified by patch testing). Symptoms/signs: pruritic papules and vesicles on an erythematous base; lichenified pruritic plaques may indicate a chronic form of the condition. Vesicles and bullae from desmolysis. No immune mediated: ● Irritant contact dermatitis (ICD) → caused by direct tissue damage following a single exposure or multiple exposures to a known irritant (body fluids, detergents, solvents, chemicals, friction); acute or chronic. Vesicles and bulla from acantholysis. ● Dyshidrosis → chronic dermatitis of the hands and feet that may cause significant physical discomfort, psychological distress and occupational impairment. Characterized by recurrent eruption of small (1-2 mm) vesicles on the palms, soles and/or lateral aspects of the fingers. ● Seborrheic eczema → papulosquamous disorder patterned on the sebum-rich areas of the scalp, face and trunk; chronic, relapsing. It may include: - Intermittent, active phases manifesting burning, scaling and itching alternating with inactive periods (activity increased in winter and early spring). - Active phases = potential secondary infection. - Candidal overgrowth. - Generalized seborrheic erythroderma. ● Stasis/varicous/venous eczema → venous insufficiency or poor circulation in the lower legs; affects people over 50 years old. Acute eczema = vesicles and crusts; chronic eczema = scale (white). ● white skin = inflammatory process → red ● black skin = inflammatory process → darker (less seeable). Squamation is easier to identify. 9 HISTOLOGICAL PHENOMENA Acute forms Chronic forms Spongiosis resulting in edema in the dermis. Reduced inflammation. Desmolysis resulting in vesicles. Acanthosis. Acantholysis resulting in vesicle/bulla. Hyperkeratosis. Acute eczema → E, V-B, E-C. Chronic eczema → E, S, F. Atopic dermatitis (immune-mediated eczema) Most common inflammatory skin disease, presented as generalized skin dryness and itchy rashes. The disease is observed in subjects with atopy (a genetic predisposition) in 50-80% of cases. The clinical aspects include evolution with subsequent reappearances, lesions depending on age and the arrangement is symmetrical. ● Initial/acute phase [1° stage eczema] → erythematous edematous, vesicular, exudative and crusted, intense itching. ● Chronic phase [2° and 3° stage eczema] → dry, infiltrated lesions; skin is wrinkled with a gray color, abrasions caused by scratching. ● 1° stage → face without mouth - convex surfaces. ● 2° stage → mouth. ● 3° stage → folds of the limbs. The 1° stage is frequent in infants (babies), present in the cheeks and forehead meanwhile the nose, lips,and nasolabial folds are spared. At or shortly after birth, atomic dermatitis may initially present as infantile seborrhoeic dermatitis involving the scalp, armpits and groin creases. Skin often feels dry and rough; with time the face, specially cheeks and flexures, becomes involved. The 2° stage is frequent in childs and covers the perioral region, antecubital creases, popliteal cables, wrists, ankles, back of the hands and neck. As children develop and grow, the distribution of dermatitis changes. With crawling, the extensor aspects of the elbows and wrists, knees and ankles are affected. The distribution becomes flexural with walking, particularly involving the antecubital and popliteal fossae (elbow and knee creases) The 3° stage is present in adults and is present at the folds of the limbs, face, back of the hands and fingers, wrists, extensor forearm. Variety of patterns. Diagnosis → ● Three major criteria: 10 ○ morphology and typical distributions = flexural lichenification or linearly in adults; facial and extensor involvement in infants and children. ○ chronic or chronically relapsing. ○ history of atopy. ○ pruritus. ● At least three minor criteria: ○ Xerosis (dry skin, gray color). ○ Ichthyosis (dry, thickened, scaly skin)/keratosis pilaris (harmless skin condition that causes dry, rough patches and tiny bumps, often on the upper arms, thighs, cheeks or buttocks; the bumps usually don’t hurt or itch). ○ Positive skin tests. ○ High levels of IgE. ○ Course influenced by environmental and/or emotional factors. ○ White dermographism. ○ Tendency to skin infections (e.g. acne). ○ Nonspecific dermatitis of the hands/feet. ○ Diaper eczema. ○ Cheilitis (inflammation of the lips). ○ Relapsing conjunctivitis. ○ Accentuation of neck folds. ○ Itching from sweating. ○ Under orbital folds Dennie-Morgan. ○ Pityriasis alba. ○ Keratoconus. ○ Cataract subcapsular. ○ Facial pallor/facial erythema. Allergic Contact Dermatitis Caused by allergic reaction to a material (allergen) that enters in contact with the skin. Characteristics of allergic dermatitis are as follows: ● Previous exposure to the allergen. ● 48-96 hours between contact and the development of changes in the skin. ● Activation of previously sensitized sites by contact with an allergen. ● Persistence of allergy for many years. ● Desmolysis. Symptoms and signs: clinical suspicion with patterned, linear or geometric shapes; anatomical restriction to hands or feet for example. Eyelids are easily affected. Patch testing may be indicated to detect allergens. The most common is the TRUE test (thin-layer rapid use epicutaneous test). Typical examples of allergic contact dermatitis: ● Eczema in the skin in contact with jewelry items due to contact allergy to nickel. ● Reactions to fragrances in perfumes. ● Localized blistering at the site of topical medications such as antibiotics. ● Swelling and blistering on exposed sites (eg, face, hands) due to contact with plants. 11 March 9th 2021 [Dermatology - Prof. Elvira Moscarella] SKIN TUMORS ● Basal cell carcinoma. ● Squamous cell carcinoma. ● Melanoma. ● Kaposi disease. ● Mycosis fungoides. ● Hemangiomas. Basal Cell Carcinoma (BCC) Nonmelanocytic skin cancer that arises from basal cells (ie, small, round cells found in the lower layer of epidermis). The prognosis for patients with BCC is excellent, but if the disease is allowed to progress it can cause significant morbidity. Metastasis is extremely rare. Most common skin cancer in caucasians. Incidence increases with increasing age and sun exposure. The DNA of certain genes is often damaged in patients with BCC; therefore, inheritance may be a factor. Most DNA alterations result from damage caused by exposure to sunlight. BCC can develop on unexposed areas (cases in the prostate have been reported). In some patients, contributing factors are exposure to or contact with arsenic, tar, coal, paraffin, certain types of industrial oil and radiation. BCC can also be associated with scars (eg, burn complications), xeroderma pigmentosum (defect in DNA repair enzymes, in which young children develop non melanoma and melanoma skin cancers due to a cellular hypersensitivity to UV radiation), previous trauma, vaccination or even tattoos. Clinical presentation Clinicopathologic types of BCC, each of which has a distinct biologic behavior include the following: ● Nodular: cystic, pigmented, keratotic; the most common type of BCC; usually presents as a round, pearly, flesh-colored papule with telangiectasia (venules cause threadlike red lines or patterns on the skin). Tend to ulcerate. ● Micronodular: not prone to ulceration; may appear yellow-white when stretched; firm to touch; may have a seemingly well-defined border. ● Infiltrative: tumor infiltrates the dermis in thin strands between collagen fibers, making tumor margins less clinically apparent; firm skin area and maybe some telangiectasia but not a nodule. Develops very deep and invasive (although slowly). ● Morpheaform (sclerotic): appears as a white or yellow waxy, sclerotic (hardening or thickening) plaque that rarely ulcerates; flat or slightly depressed, fibrotic and frim. Looks like a scar. ● Superficial: seen mostly on the upper trunk or shoulders; appears clinically as an erythematous; well circumscribed patch or plaque (pigmented or not . if not it is a scaly red erythematous with elevated borders, sometimes crust) ; often a withish scale. 14 Dermoscopy helps management: useful to define lesion subtype, to detect the presence of clinically non visible pigmentation, to guide treatment choice. middle patient: non invasive. third patient: surgical removal. first: surgical removal. Factors related to the patient are age, performance status, compliance and pre-existing syndromes. In nearly all cases of BCC, surgery is the recommended treatment modality. Techniques used include the following: ● Electrodesiccation and curettage. ● Excisional surgery. ● Cryosurgery. Radiation therapy is considered when many lesions are present. Hedgehog Inhibitors (HHI): If we block the PTCH pathway we are blocking the basal cell carcinoma growth; because of the high cost it is done when a surgery or radiotherapy are not possible in very advanced cases. Targeted therapy: vismodegib, sonidegib. Side effects are reversible after discontinuation. Recurrence rate is a limitation. Keratinocyte Skin Cancer Increased interest in the progression model of AK (actinic keratosis, crusty, scaly growth) towards SCC (squamous cell carcinoma). Improved knowledge of dermoscopy features of AK and SCC. 15 Malignant transformation of normal epidermal keratinocytes is the hallmark of cSCC. One critical pathogenic event is the development of apoptotic resistance through functional loss of TP53 (tumor suppressor gene). TP53 mutations are seen in over 90% of skin cancers diagnosed in the United States, as well as in most precursor skin lesions, suggesting that loss of TP53 is an early event in the development of cSCC. UVR causes DNA damage through the creation of pyrimidine dimers, which results in the genetic mutation of TP53. Upon subsequent UVR exposure, keratinocytes undergo clonal expansion, acquiring further genetic defects that ultimately lead to invasive cSCC. Risk factors include the following: ● UVR exposure → skin types 1 or 2 specially. ● Immunosuppression → radiotherapy or after supportive treatment for organ transplantation. ● Exposure to ionizing radiation or chemical carcinogens. ● Human papillomavirus (HPV) infection. SCC occurs in men 2-3 times more frequently than it does in women, most likely as a result of higher accumulative lifetime UV exposure in men. This increased exposure may be due to greater participation by men in occupations that entail more significant exposure to sunlight or to other occupational hazards, such as soot, oils or tars. The typical age of presentation for SCC is approximately 70 years. This varies widely, however, and in certain high-risk groups (eg, organ transplant recipients, patients with epidermolysis bullosa, AK) where SCC often manifests at a much younger age. Squamous cell carcinoma in situ (CIS), sometimes referred to as Bowen disease, is a precursor to invasive cSCC. Characteristics of this lesion include nuclear atypia, frequent mitoses, cellular pleomorphism and dyskeratosis, parakeratosis and hyperkeratosis. Usually a plaque or a patch not pigmented with scales and no micro-ulceration. Conventional cSCC can be divided into the following four histologic grades, based in the degree of nuclear atypia and keratinization found: ● Well differentiated → characterized by more normal appearing nuclei with abundant cytoplasm and extracellular keratin pearls. ● Moderately differentiated → exhibits features that are intermediate between well-differentiated and poorly differentiated lesions. ● Poorly differentiated → shows high degree of nuclear atypia with frequen mitoses, a greater nuclear-cytoplasmic ratio and less keratinization. ● Highly undifferentiated → shows epithelial cells that may be difficult to distingish from mesenchymal, melanoma or lymphoma cells. Prognosis. Although primary cSCC is not often fatal, it can cause significant morbidity if left untreated. Most cSCCs are located in the facial and head-and-neck region, where surgery for advanced-stage disease can be disfiguring. Even if the tumor invades the lymph nodes, it is still curable. Invasive tumors tend to be the least differentiated and bigger. 16 Cutaneous melanoma is a malignant tumor deriving from melanocytes, which arise from the neural crest and migrate to the epidermis, uvea, meninges and ectodermal mucosa. Melanocytes reside in the skin and produce melanin, they are contained within the basal layer of epidermis, at the junction of dermis and epidermis. Melanomas may develop in or near a previously existing lesion (a nevus, the benign melanocytic tumor) or in healthy-appearing skin. Melanoma developing from healthy skin is said to arise “de novo”, without evidence of a precursor lesion; they account for the majority of cases. About 30% of melanomas arise from a pre-existing nevus, often a congenital nevus or one that has long been stable. Pathophysiology The sequence of events in which normal melanocytes transform into melanoma cells, referred to as melanomagenesis, is poorly understood. It likely involves a multistep process of progressive genetic mutations that: 1. alter cell proliferation, differentiation and death; 2. impact susceptibility to carcinogenic effects of ultraviolet radiation. There are multiple pathways of melanoma pathogenesis, with melanomas in sun-protected skin (trunk) developing in association with a high nevus count and intermittent ultraviolet radiation as opposed to those developing on sun-exposed skin in patients with low nevus counts and chronic sun exposure. Differences in frequency of BRAF, NRAS or c-Kit mutations are also related (eg, acral sites, mucosal sites), since they are associated to specific patterns of the disease and risk factors. alterations and melanoma subtypes Distinct patterns of mutations in melanoma driver genes, BRAF, NRAS, c-KIT, have been demonstrated to correlate with the site of the primary tumor, the degree of chronic sun-induced damage, the histological subtype and age. Etiology/Causes: 19 The incidence of malignant melanoma has been increasing rapidly worldwide, and this increase is occurring at a faster rate than any other cancer except lung cancer in women. Melanoma shows increased worldwide incidence in fair-complexioned individuals living in sunny climates and nearer the equator, suggesting a causative role for ultraviolet radiation. Most data support the hypothesis that melanoma development is related to intermittent, intense sun exposure, particularly in childhood or adolescence. In contrast, chronic sun exposure does not appear to confer increased risk, except for the more UV-related melanoma subtypes (lentigo maligna). Use of tanning beds has also increased risk of melanoma in young patients. ● Presence of xeroderma pigmentosum or familial atypical mole melanoma → 500 to 1000-fold greater relative risk of developing melanoma. ● Clinical atypical/dysplastic nevi in familial melanoma. ● Sporadic (nonfamilial) clinical atypical/dysplastic nevi (particularly >5-10). ● Melanoma in first-degree relatives (especially multiple). ● Large numbers of common nevi (>100) = multiple nevi. ● Previous melanoma. ● Male sex. ● Age older than 50 years. The average age at diagnosis is 57 years and up to 75% of patients are younger than 70 years. ● Sun sensitivity/history of excessive sun exposure of sunburns. ● Large (giant) congenital nevi (>20 cm in diameter in an adult). A fair-skin phenotype (blue/green eyes, blond or red hair, light complexion, sun sensitivity) and the occurrence of blistering sunburn(s) in childhood and adolescence are universal risk factors for melanoma. Individuals with these traits have been the focus of preventive efforts worldwide. Pregnancy or hormonal therapy with oral contraceptives or hormonal replacement does not appear to be a risk factor for melanoma development. Clinical Presentation A new changing mole or blemish is the most common warning sign for melanoma. Variation in color and/or an increase in diameter, height or asymmetry of borders of a pigmented lesion are noted by the majority of patients with melanoma at the time of diagnosis. Symptoms such as bleeding, itching, ulceration and pain in a pigmented lesion are less common but warrant an evaluation. Since the majority of cutaneous melanoma arises de novo, routine sampling or mass removal of stable-appearing melanocytic nevi is not warranted for melanoma prevention. However, individuals with numerous moles or a family history of melanoma are at increased risk of developing melanoma and should be followed. Diagnosis → dermoscopy; non-invasive technique that allows visualization of surface and subsurface structures of the skin. ABCDE Rules: ● Asymmetry → half the lesion does not match the other half. 20 ● Border irregularity → the edges are ragged, notched or blurred. ● Color variegation → pigmentation is not uniform and may display shades of tan, brown, black; white, reddish or blue discoloration is of particular concern. ● Diameter → greater than 6 mm is characteristic, although some melanomas may be smaller in size; any growth in a nevus warrants an evaluation. ● Evolving → changes in the lesion over time are characteristic; this factor is crucial for nodular or amelanotic (nonpigmented) melanoma, which may not exhibit the ABCD criteria above. Physical Examination: Melanoma occurs most commonly on the trunk in white males and lower legs and back in white females. In African American, Hispanic and Asian individuals, the most common site is the plantar foot, followed by subungual, palmar and mucosal sites. Melanoma can occur on any skin or mucosal surface, although history of cutaneous melanoma does not appear to increase the risk of developing primary intraocular, oral or other mucosal melanoma. Histopathological Examination The standard criteria for melanoma diagnosis is histopathological examination of clinically suggestive skin or mucosal lesions, this exam is made through excision of the lesion and histological biopsy. An excisional biopsy with narrow margins is preferred and may consist of a fusiform/elliptical excision, an excisional punch biopsy, or a saucerization/deep shave biopsy (into the deeper reticular dermis), the latter of which is the most common technique used. 21 Staging Prognosis depends on the disease stage at diagnosis. According to SEER, 5-year relative survival rates are as follows: ● localized (confined to primary site) = 98.5%. ● regional (spread to regional lymph nodes) = 62.9%. ● distant (metastatic) = 19.9%. ● Stage 0 → in situ tumor. ● Stage I and II → localized disease; the finding of ulceration in the primary tumor allows differentiating stage I or II “a” from “b” and “c”. ● Stage III → regional disease; regional lymph node ultrasound is performed. This stage includes occult and clinically detected metastasis into regional lymph nodes and also “in transit” and “satellites”. Clinical occult metastasis are diagnosed histologically after sentinel lymph node biopsy or lymph node dissection. ● Stage IV → distant metastasis; metastasis to other organs (lung, brain, liver, kidney, etcc) as well as to distant skin, subcutis and lymph nodes. CT scan is performed. The most common clinically apparent sites of distant metastases in melanoma patients are: skin, lung, brain, liver, bone, and intestine. 24 Current NCCN guidelines do not recommend surveillance (follow-up) laboratory or imaging studies for asymptomatic patients with stage IA, IB. Imaging studies (CT and/or PET-CT) should be obtained as clinically indicated for confirmation of suspected metastasis or to delineate the extent of disease and may be considered to screen for recurrent/metastatic disease in patients with stage IIA-IV disease, although this latter recommendation remains controversial. Routine laboratory or radiologic imaging in asymptomatic melanoma patients of any stage is not recommended after 3-5 years of follow-up. Therapy ● Stage 0 → excision. ● Stage I and II → excision, with or without lymph node management. ● Resectable stage III → excision, with or without lymph node management; adjuvant therapy and immunotherapy. ● Unresectable stage III, stage IV and recurrent melanoma → intralesional therapy, immunotherapy, targeted therapy if a BRAF V600 mutation is present. Chemotherapy if the patient does not respond to previous treatments. Targeted therapy is preferred. For immunotherapy, PD-1 inhibitor monotherapy with pembrolizumab or nivolumab is recommended, or the combination of nivolumab with ipilimumab. Mutation Status of Cutaneous Melanoma Activation of the BRAF pathway is implicated in promoting growth, proliferation and differentiation of cells. The most common mutation is V600E (substitution of glutamic acid for valine at p. 600); this mutation will result in 10 times more kinase activity so will act as an oncogene, promoting cell growth, differentiation and survival. 25 BRAF inhibitors improve overall and progression-free survival in patients with advanced melanoma with the V600E mutation; so identifying this mutation in patients is now of critical therapeutic importance. Kaposi Sarcoma Spindle-cell tumor thought to be derived from endothelial cell lineage. This condition carries a variable clinical course ranging from minimal mucocutaneous disease to extensive organ involvement. Kaposi sarcoma can be primarily categorized into 4 types: ● Epidemic of AIDS-related. ● Immunocompromised. ● Classic/sporadic. ● Endemic (African). Cutaneous lesions: ● May occur at any location but typically are concentrated on the lower extremities and the head and neck region. ● Lesions may have macular, papular, nodular or plaquelike appearances. ● Nearly all lesions are palpable and nonpruritic. ● Lesions may range in size from several millimeters to several centimeters in diameter. ● Lesions may assume a brown, pink, red or violaceous color and may be difficult to distinguish in dark-skinned individuals. ● Lesions may be discrete or confluent and typically appear in a linear, symmetrical distribution, following Langer lines. ● Mucous membrane involvement is common (palata, gingiva, conjunctiva). 26 Lesion involves up to 10% of the body surface → stage IA. Lesion involves 10% or more of the body surface → stage IB. Many cases remain at these stages for many years or decades without further progression. Stages IIA and IIB Clinical lymphadenopathy may develop (stage IIA), sometimes with progression of the plaques to form tumors (stage IIB), or tumors may form from plaques in the absence of lymphadenopathy (stage IIB). Either process usually takes years, or even decades, to develop. Once tumors form, they are prone to ulceration. D’Emblee Mycosis Fungoides Tumour d' emblee is the term used for the patient presenting with skin tumors not preceded by patches or plaques. Sudden multifocal development of tumors of apparent mycosis fungoides may rarely occur without preceding patches or plaques. Most, if not all, of such cases probably represent primary cutaneous CD30+ pleomorphic, medium or large cell T cell lymphomas. Stage III (Erythrodermic Mycosis Fungoides) Mycosis fungoides that are evident as an erythroderma but with too few circulating lymphocytes to warrant a diagnosis of Sézary syndrome are designated erythrodermic mycosis fungoides. Dermatopathic lymphadenopathy is present in these cases. Rarely, such patients may present with a nodulotumorous eruption. Stages IVA and IVB Development of lymph nodes that are histologically positive for tumor (stage IVA) and/or visceral lesions (stage IVB) may occur rather rapidly after tumor-stage disease develops and/or clinical lymphadenopathy is detected. Alternatively, either or both may arise from erythrodermic disease (stage III) at a very variable rate. Poor prognosis. 29 Sézary Syndrome The combination of erythroderma and leukemia is defined as Sézary syndrome. However, different clinicians use different criteria regarding the number of circulating atypical lymphocytes sufficient to warrant this diagnosis. According to some, the diagnosis is established in an erythrodermic patient if more than 5% of peripheral lymphocytes are atypical. Others use the absolute number of atypical lymphocytes in peripheral blood (>1000/μL). In obvious cases, some use a quick and easy criterion of greater than 10 CD4+ T cells for every CD8+ T cell. Lymphadenopathy is usually present, and the skin itself is usually edematous. Other frequently observed changes include palmar and/or plantar hyperkeratosis, alopecia, nail dystrophy and ectropion. Hepatosplenomegaly may be present. As in other forms of mycosis fungoides, a nonspecific dermatitis and/or pruritus may precede the disease. Transformation of the disease to a more aggressive form is common. It may occur in lymph nodes even as skin lesions are showing improvement or a response to treatment. Treatment Mycosis fungoides treatment selection should be based on the stage and previous treatment history. In general, topical therapies are indicated for stage I patients and systemic therapies or combinations of topical and systemic therapies are indicated for patients with stage IIB disease or greater, or for patients with stage I mycosis fungoides who are intolerant of topical treatments or whose condition has failed to respond to such treatments. Infantile Hemangiomas Infantile hemangiomas are the most common benign tumors of infancy, occuring in up to 10% of infants, with up to 50% appearing in the head and neck. Infantile hemangiomas are made up of blood vessels that form incorrectly and multiply more than they should. These blood vessels receive signals to grow rapidly early in a baby’s life. 30 They may be present at birth and often become apparent within the first few months of life. Risk factors for infantile hemangiomas include female sex, being of Northern European descent, prematurity, multiple gestation, older maternal age, maternal progesterone use, placenta previa and preeclampasia. 75-90% have a single hemangioma, usually on the head or neck. They also may be segmental or multifocal. Usually, these hemangiomas are noticed at approximately 2-3 weeks of life. The initial proliferative phase usually lasts for about 1 year, with rapid growth during the first 4 months. This is followed by gradual involution over several years, with >90% involuting completely by age 10. Although infantile hemangiomas involute with time, residual skin changes, such as telangiectasia, scarring, atrophy and fibrosis persist in up to 30% lesions after involution is complete. Focal/localized infantile hemangiomas are discrete papules, nodules or plaques that appear to arise from a central focus. Segmental infantile hemangiomas are small large plaques that affect an embryological or developmental segment of the body. Often have many surface telangiectasias and irregular, ill-defined borders. Precursor lesions may present at birth or early infancy as any combination of fine telangiectasias, areas of pallor, erythema, ecchymoses and sometimes ulcerations. Hemangiomas appear distinctly depending upon the depth of the lesion: ● Superficial → bright red, dome-shaped vascular papules, plaques or nodules. ● Deep → usually noted at 3-6 months of age as subcutaneous firm to rubbery, compressible, bluish, vascular plaques or nodules with an overlying venous network or telangiectasia. ● Mixed → has features of both. Regressing superficial hemangiomas are soft and will be marked by a color change from bright red to dull red, and there may be central graying. Regression of deep infantile hemangiomas is first recognized by softening of the originally firm and rubbery deep component. Differential Diagnosis ● Congenital hemangioma (CH) → fully formed vascular tumors at birth; two main types are: rapidly involuting congenital hemangiomas (RICH) and non-involuting congenital hemangiomas (NICH), and variants have been reporter. The proliferative phase in these tumors occurs in utero, and typically do not proliferate postnatally as seen with infantile hemangiomas. CHs are characterized by hemispheric pink to purple vascular plaques with overlying telangiectasia and the characteristic peripheral rim of pallor. 31 Pyodermas Pyoderma is a cutaneous infection with pyogenic (pus-forming) bacteria. Although the term pyoderma literally means “pus in the skin”. Pus: exudate, typically white-yellow fluid formed at the site of inflammation during bacterial or fungal infection. Protein-rich fluid and dead leukocytes (immune response mostly neutrophils). ● Superficial → pyoderma of the hair follicle which include superficial folliculitis, folliculitis (sycosis barbae), furuncle (boil) and carbuncle. Superficial pyoderma of the skin include impetigo and bullous impetigo. ● Invasive infections → lymphangitis, lymphadenitis, erysipelas, cellulitis, streptococcal gangrene. ● Staphylococcal toxin-associated syndromes → staphylococcal scarlet fever, staphylococcal scalded-skin syndrome, staphylococcal toxic-shock syndrome. Pyodermas of the Hair Follicle Folliculitis is a pyoderma that begins within the hair follicle. It is classified according to the depth of invasion (superficial or deep) and microbial etiology. A small, fragile, dome shaped pustule occurs at the infundibulum (ostium or opening) of a hair follicle, often on the scalps of children and in the beard area, axillae, extremities and buttocks of adults. S. aureus is the most commonly involved germ, other agents are gram negative bacteria and fungi. 34 Sycosis barbae is a deep folliculitis with perifollicular inflammation occurring in the bearded areas of the face and upper lip. If untreated, the lesions may become more deeply seated and chronic. Dermatophytic folliculitis (fungal) must be differentiated from S. aureus folliculitis. In fungal infections, hairs are usually broken or loosened, and there are suppurative or granulomatous nodules rather than pustules. Treatment → local antibiotics (mupirocin or topical clindamycin); extensive cases require systemic antibiotic therapy. Furuncle or boil is a deep-seated inflammatory nodule that develops around a hair follicle, usually from a preceding, more superficial folliculitis and often evolving into an abscess. It starts as a hard, tender, red folliculocentric nodule in hair-bearing skin that enlarges and becomes painful and fluctuant after several days (ie, undergoes abscess formation). Rupture occurs with discharge of pus, and often a core of necrotic material. Pyodermas of the Skin Impetigo is a common and highly contagious infection of the superficial skin. It usually arises from the mouth/sites of bacterial accumulation in the body; yellow crust; very contagious for yourself and from one person to another person. Very common among children with poor hygiene, or during summertime. Secondary infections are more frequent (combined with eczema). Clinical diagnosis: peri-orifical forms are usually de to streptococcal stereotypes different from those of the angina; ab anti SBEA only for confirmation of a post streptococcal glomerulonephritis Treatment → systemic antibiotics. Two common clinical patterns are recognized: bullous and nonbullous (>70% of cases). In industrialized nations, nonbullous impetigo is most commonly caused by S. aureus and less often by group A Streptococcus. Group A Streptococcus remains a common cause of nonbullous impetigo in developing nations. In a typical sequence, S. aureus spreads from nose to normal skin (approximately 11 days later) and then develops into skin lesions (after another 11 days). Conditions that disrupt the integrity of the epidermis, providing a portal of entry of impetiginization are insect bites, epidermal dermatophytosis, herpes simplex, varicella, abrasions, lacerations and thermal burns. The initial lesion is a transient vesicle or pustule that quickly evolves into a honey-colored crusted plaque that can enlarge to greater than 2 cm in diameter. Surrounding erythema may be present. Constitutional symptoms are absent. Regional lymphadenopathy may be present in up to 90% of patients with prolonged, untreated infection. If untreated, the lesions may slowly enlarge and involve new sites over several weeks. 35 Bullous impetigo occurs more commonly in the newborn and in older infants, and is characterized by rapid progression of vesicles to flaccid bullae. Caused by toxins produced by phage group II S. aureus (exfoliatine). In a study of bullous impetigo, 51% of patients had concurrent S. aureus cultured from the nose or throat, and 79% of cultures grew the same strain from both sites. Bullae usually arise on areas of grossly normal skin. The Nikolsky sign (sheet-like removal of epidermis by shearing pressure) is not present. Bullae initially contain clear yellow fluid that subsequently becomes dark yellow and turbid, and their margins are sharply demarcated without an erythematous halo. They are superficial and rupture and collapse within a day or two, sometimes forming thin, light-brown to golden-yellow crusts. Impetiginization → superinfection by S. aureus (phage group II) of other lesions. SSSS (staphylococcal scalded skin syndrome) due to staphylococcal toxin: ● Generalized exanthematous disease consisting of cutaneous tenderness and widespread superficial blistering and denudation. ● Individuals initially have a faint, orange-red macular exanthem or uniform erythema sparing mucosal surfaces in association with a purulent conjunctivitis, otitis media, nasopharyngeal infection or, occasionally, pyogenic skin infections such as bullous impetigo or that which arises from an umbilical stump or boil (carbuncle). ● Nikolsky sign: stroking the skin results in a superficial blister. ● Periorificial and flexural accentuation of the exanthema is often noted. ● Tenderness can often be so severe that infants will refuse to lie down. ● The disease looks very worrisome, resembling a generalized scalding burn. ● Fevers are often present; children usually do not appear toxic unless they have developed complications such as septicemia or pneumonia. ● Process usually resolves spontaneously or faster with antibiotics and superficial desquamation, with healing completed within 5-7 days. ● Blisters obtained from intact blisters are usually sterile, consistent with the pathogenesis of a hematogenously disseminated toxin originating from a distant focus or infection. Deep Pyoderma Ecthyma is a cutaneous pyoderma characterized by thickly crusted erosions or ulcerations. It is usually a consequence of neglected impetigo and classically evolves in impetigo occluded by footwear and clothing. Most commonly on the lower extremities of children, neglected elderly patients or individuals with diabetes. Poor hygiene and neglect are key elements in pathogenesis. Erysipelas is caused by group A streptococcus. ● Painful, edematous erythema with sharp margination. There is tenderness, the patient has fever and chills. ● Skin and soft tissue infections (SSTI) are characterized by clinical findings that include an acute, tender, spreading, edematous, suppurative inflammation of the skin, subcutaneous fat, often associated with systemic symptoms. 36 Present in mucosal tissues in adults and children (may be present in other parts of the body as well, as for example hands). In children with hpv in the genital area we must suspect sexual abuse. ● Papules of variable size with a rough scaly surface. ● Caused by human papillomaviruses (HPV), a subset of which are associated with cervical, penile, anal and other epithelial malignancies. ● Treatment often requires physical or immune-mediated destruction of infected epithelial cells. ● A prophylactic vaccine effectively protects from infection with HPVs most commonly identified in cervical cancer and genital warts. ● Common warts are usually multiple, confluent, keratotic papules. Epidemiologic and molecular studies confirm that infection with high-risk HPVs is the cause of most cervical cancers. The prophylactic HPV vaccine represents the newest approach to preventing genital HPV infection. The vaccine, which is noninfectious, is based on self-assembly of the L1 protein into virus-like particles (VLPs) that morphologically and antigenically resemble authentic viral capsids. Gianotti-Crosti Disease Papular acrodermatitis of childhood; common, self-limited dermatosis. Characterized by monomorphic dome-shaped or flat topped papules symmetrically distributed on face and extensor extremities. Associated with multiple viral triggers and immunizations. Historically associated with hepatitis B infection, but now more often triggered by Epstein-Barr virus. Cutaneous lesions evolve over a few days and last for 2-8 weeks. Erythema Infectiosum (Parvovirus B19) ● Causes erythema infectiosum, fifth disease. ● Fifth disease in children with “slapped cheeks” followed by an erythematous, lacy eruption on the trunk and extremities. ● Symmetric polyarthritis, particularly of the small joints. ● Causes papular purpuric gloves-and-socks syndrome with pruritic erythema, edema and petechiae of the hands and feet, fever and oral erosions in adolescents. ● Aplastic crisis in patients with increased red blood cell turnover, chronic anemia in immunocompromised persons, and fetal hydrops. Hand-Foot-Mouth Disease (Coxsackie A Virus) ● Viral exanthem seen most commonly in children in summer and fall. ● Erosions in the mouth and papulovesicles on the palms and soles. ● Caused by enteroviruses including coxsackievirus A 16 and enterovirus 71. ● Self-resolving without serious sequelae in the majority of cases but may have serious complications when caused by enterovirus 71. Nearly all cases of HFMD have painful oral lesions. These are generally few in number and are found on the tongue, buccal mucosa, hard palate and, less frequently, the oropharynx. 39 The lesions start as bright pink macules and papules that progress to small 4-8 mm vesicles with surrounding erythema. These quickly erode and form yellow to gray erosions surrounded by an erythematous halo. Parasitosis ● Scabies. ● Phthirus pubis. ● Pediculosis. Scabies ● Human infestation caused by host-specific itch mite that lives its entire life cycle within the epidermis. ● Causes a diffuse, pruritic eruption after an incubation period of 4-6 weeks. ● Transmitted by close physical contact or by fomites. ● Topical therapy is most popular, but oral ivermectin is effective. ● Because of the common occurrence of asymptomatic mite carries in the household, all family members and close contacts should be treated simultaneously. ● Several thread-like burrows are present in the web spaces of the fingers and on the knuckles, a common location for these lesions in scabies. Longitudinal scraping of a burrow will often reveal the mite or mite products under microscopic examination. Pediculosis Pubis ● Best to call “crab lice” rather than “public lice” as infestations may involve other hair-bearing sites such as mustache, beard, axillae, eyelashes, eyebrows and scalp hair. ● Transmitted by sexual or close contact as well as via fomites (contaminated clothing, towels and bedding). ● Topical therapy options similar to pediculosis capitis, but ivermectin orally is preferred. Pediculosis Capitis (Head Lice) ● Infestation occurs worldwide affecting hairs of the scalp most commonly children between the ages of 3 and 12. ● Presence of 0.8 mm eggs (nits) attached to scalp hairs is the most common sign of infestation. ● Spread by close physical contact and sharing of headgear, combs, brushes, and pillows. ● Resistance to traditional over-the-counter preparations is growing, topical malathion and ivermectin should be considered in resistant cases. It is important that everybody that has been in contact with the patient or that live in the same house and have contact often are treated for the mite, since they can be asymptomatic carriers of the parasite. Also wash everything that can be washed with warm water and what cannot be washed should be thrown away. Without humans the mite lives only up to a week. Superficial Fungal Infection 40 ● Dermatophyte species are contained in three genera: Epidermophyton, Microsporum and Trichophyton. They are divided further according to three natural habitats (humans, animals and soil). ● Dermatophytes infect keratinized tissue including skin, hair and nails. ● Microscopic examination, culture, Wood’s light evaluation and histopathology may all be useful in confirming a dermatophytosis. ● Trichophyton is the most common species isolated in the US. ● Several topical preparations (imidazoles and allylamine) and oral agents (griseofulvin, itraconazole, uconazole, and terbinafine) serve as effective antifungal therapeutic options for dermatophytoses. Tinea Pedis ● Chronic hyperkeratotic tinea pedis → the hyperkeratotic type of tinea pedis is characterized by chronic plantar erythema with slight scaling to diffuse hyperkeratosis. This type can be asymptomatic or pruritic. Also called moccasin tinea pedis, because of its moccasin-like distribution. Both feet are usually affected. Typically, the dorsal surface of the foot is clear, but in severe cases the condition may extend onto the sides of the foot. Tinea manuum is often unilateral and associated with moccasin-type tinea pedis (2-feet-1-hand syndrome). One study suggests the scratching habits of the infected individual result in transmission of the dermatophytes from the feet to the hand. ● Inflammatory/vesicular tinea pedis → painful, pruritic vesicles or bullae, most often on the instep or anterior plantar surface. The lesions can contain either clear or purulent fluid; after they rupture, scaling with erythema persists. Cellulitis, lymphangitis and adenopathy can complicate this type of tinea pedis. The inflammatory/vesicular type can be associated with an eruption called the dermatophytid reaction, which develops on the palmar surface of one or both hands and/or the sides of the fingers. Papules, vesicles and occasionally bullae or pustules may occur, in a symmetrical fashion, and it may mimic dyshidrosis (pompholyx). This is an allergy or hypersensitivity response to the infection of the foot, and it contains no fungal elements. The specific explanation of this phenomenon is still unclear. Distinguishing between a dermatophytid reaction and dyshidrosis can be difficult. Dermatophytid reactions are associated with vesicular tinea pedis; therefore, a close inspection of the feet is necessary in patients with vesicular hand dermatoses. The dermatophytid reaction resolves when the tinea pedis infection is treated, and treatment of the hands with topical steroids can hasten resolution. Lesions begin as red papules with progression to grayish ring-formed patches containing perifollicular papules. Pustules with inflamed crusts, exudate, matted infected hairs and debris may be seen. Inflammatory tinea capitis caused by Microsporum canis (Kerion Celsi) usually present with alopecia, inflammatory papules and nodules; lymphadenopathy may be present. 41 Pityriasis (Tinea) Versicolor Tinea versicolor is a common, benign, superficial cutaneous fungal infection usually characterized by hypopigmented or hyperpigmented macules and patches on the chest and the back. Tinea versicolor is caused by the dimorphic, lipophilic organisms in the genus Malassezia, formerly known as Pityrosporum. Fourteen species are recognized within this classification of yeasts, of which Malassezia globosa, Malassezia sympodialis, and Malassezia furfur are the predominant species isolated in tinea versicolor. Malassezia is extremely difficult to propagate in laboratory culture and is culturable only in media enriched with C12- to C14-sized fatty acids. Malassezia is naturally found on the skin surfaces of many animals, including humans. Indeed, it can be isolated in 18% of infants and 90-100% of adults. The organism can be found on healthy skin and on skin regions demonstrating cutaneous disease. In patients with clinical disease, the organism is found in both the yeast (spore) stage and the filamentous (hyphal) form. Factors that lead to the conversion of the saprophytic yeast to the parasitic, mycelial morphologic form include a genetic predisposition; warm, humid environments; immunosuppression; malnutrition; pregnancy; and Cushing disease. There are sharply marginated, uniformly hypopigmented macules (oval to round patches) with fine, sometimes barely perceptible scales, which are easily scraped off with a glass slide. When the lesions are very large they can be confused with vitiligo. Pityriasis Rosea (of Gilbert) Benign rash, the name means “fine pink scale”. It is a common skin disorder observed in otherwise healthy people, most frequently children and young adults. Pityriasis rosea manifests as an acute, self-limiting, papulosquamous eruption with a duration of 6-8 weeks. It evolves rapidly, usually beginning with a patch that heralds the eruption (“herald patch”). It may sometimes occur in atypical variants or may mimic other skin disorders, such as tinea corporis and secondary syphilis. The disease typically begins with a solitary patch, usually salmon-colored, that heralds the eruption and thus is commonly referred to as the herald patch or spot. This initial lesion enlarges over a few days to become a patch with a collarette of fine scale just inside the well-demarcated border. Dermoscopy evaluation using a triple-light source may be useful. Within the next 1-2 weeks, a generalized exanthem usually appears, although it may occur from hours to months after the herald patch. This secondary phase consists of bilateral and symmetric macules with a collarette scale oriented with their long axes along cleavage lines. 44 This phase tends to resolve over the next 6 weeks, but variability is common and occasionally persistent. Pruritus is commonly evident in 25-75% of patients and usually of mild-to-moderate severity. Secondary eczematous changes can occur if pruritus is severe. A small number (approximately 5%) of patients with pityriasis rosea have mild prodromal symptoms (eg, malaise, fatigue, headache, nausea, anorexia, chills, fever, and arthralgias) that precede the appearance of the herald patch. Lymphadenopathy may occur before the onset of the rash. Pityriasis rosea (PR) has often been considered to be a viral exanthem, a view supported by the condition’s seasonal occurrence, its clinical course, the possibility of epidemic occurrence, the presence of occasional prodromal symptoms, and the low rate of recurrence. The primary plaque is seen on the skin in 50-90% of cases a week or more before the onset of the eruption of smaller lesions. This secondary eruption occurs 2-21 days later in crops following the lines of cleavage of the skin. On the back, this eruption produces a “Christmas tree” pattern. Pityriasis rosea (PR) is a self-limited disease; treatment is supportive. Sweat, and soap that may cause irritation and should be avoided early in the disease. Topical zinc oxide and calamine lotion are useful for pruritus. If the disease is severe or widespread (eg, vesicular pityriasis rosea), topical or oral steroids may be used. Syphilis Sexually transmitted disease caused by the spirochete bacterium Treponema pallidum, characterized by a chronic intermittent clinical course. Treponema pallidum is transmitted person to person via direct contact with a syphilis ulcer during vaginal, anal or oral sex and may enter through the skin or mucous membranes. The locations for syphilitic ulcers include the vagina, cervix, anus, penis, rectum, lips, hands and inside of the mouth. Usually classified into 4 stages: primary, secondary, latent and tertiary. It can be either acquired or congenital. It can be transmitted either by intimate contact with infectious lesions (most common) or via blood transfusion (if blood has been collected during early syphilis), and it can also be transmitted transplacentally from an infected mother to her fetus. 45 Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in advanced stages. → “the great imposter”. Complex and variable manifestations. Acquired early syphilis: ● Primary syphilis → incubation period is usually between 14 and 28 days with a range of 9-90 days. The primary lesion or chancre develops at the site of infection, usually in the genital area. A dull red macule develops, becomes papular and then erodes to form an indurated ulcer (chancre). The draining inguinal lymph nodes may become moderately enlarged, mobile, discrete and rubbery. The chancre and the lymph nodes are both painless and non.tender, unless there is concurrent or secondary infection. Without treatment, the chancre will resolve within 2-6 weeks to leave a thin atrophic scar. Chancres may develop on the vaginal wall and on the cervix. Extragenital chancres are found in 10% of patients, affecting sites such as the fingers, lips, tongue, tonsils, nipples, anus or rectum. Anal chancres often resemble fissues and may be painful. ● Secondary syphilis → 6-8 weeks after the development of the chancre when the treponemes disseminate to produce a multisystem disease. Constitutional features such as mild-fever, malaise and headache are common. Over 75% of patients present with a rash on the trunk and limbs that they may later involve the palms and soles; this is initially macular but evolves to maculo-papular or papular forms, which are generalized, symmetrical and non-irritable. 46 Stigmata are the result of treponemal infection causing permanent tissue damage to the fetus in utero or to the baby after birth or in either the early or the late stage. ● Hutchinson’s incisors (anterior-posterior thickening with notch on narrowed cutting edge); ● Mulberry molars (imperfectly formed cusps/deficient dental enamel); ● High arched palate; ● Maxillary hypoplasia; ● Saddle nose (following snuffles); ● Rhagades (radiating scars around mouth, nose and anus following rash); ● Salt and pepper scars on retina (from choroiditis); ● Sabre tibia (from periostitis); ● Bossing of frontal and parietal bones (healed periosteal nodes). Serological Tests for Syphilis ● Non-treponemal (non-specific) tests → venereal diseases research laboratory (VDRL) test; rapid plasma region (RPR) test. ● Treponemal (specific) antibody tests → treponemal antigen-based enzyme immunoassay (EIA) for IgG and IgM; T. pallidum hemagglutination assay (TPHA); T. pallidum particle agglutination assay (TPPA); fluorescent treponemal antibody-absorbed (FTA-ABS) test. Positive RPR and VDRL needs to be confirmed by fluorescent treponemal antibody/absorption (FTA-ABS) or TPPA. VDRL results turn positive 1-2 weeks after chancre formation. Nontreponemal tests usually become nonreactive with time after treatment. Serology values in patients with HIV infection may take longer to fall than in patients without HIV infection. In some patients, nontreponemal antibodies can persist, sometimes for life, a condition referred to as “serofast”. Because of the possibility of false-positive results, confirmation for any positive or equivocal nontreponemal test result should follow with a treponemal test, such as FTA-ABS. Treatment of syphilis: ● Penicillin is the drug of choice. ● Doxycycline is the best alternative for treating early and late latent syphilis. Syphilis associated with HIV infection does not require any enhanced antimicrobial therapy. ● Reinfection rates among MSM are high, so frequent serological testing in this group is recommended. ● Use of the RPR-based screening algorithm. When there is a low epidemiologic risk or clinical probability of syphilis, the positive predictive value of an isolated unconfirmed reactive treponemal chemiluminescence test or enzyme immunoassay is low. Chancroid Bacterial sexually transmitted disease caused by infection with Haemophilus ducreyi. It is characterized by painful necrotizing genital ulcers that may be accompanied by inguinal lymphadenopathy. 49 The bacterium enters the skin through disrupted mucosa and causes a local inflammatory reaction. It produces a cytocidal distending toxin that appears to be responsible for its destructive effects. Highly contagious and infectious but curable; pathogenic only in humans, with no intermediary environmental or animal host. Chancroid was once highly prevalent in many areas, but collaborative efforts in increasing social awareness and subsequent changes in sexual practices, along with improved diagnosis and treatment options, have eradicated chancroid as an endemic disease in industrialized countries. In 2000, the proportion of chancroid among genital ulcerative diseases (GUD) decreased from 69% to 15%. It remains prevalent in underdeveloped regions. Ulcerative STDs penetrate the skin of the external genitalia, colonize the subcutaneous tissue and produce tissue damage, causing ulceration. Skin abrasion and microtrauma is necessary to penetrate normal skin. The disruption of the mucosal barrier increases the risk of HIV access to the bloodstream and inflammatory cells and serves as a focus for bacterial and viral shedding. Ulcerative STDs increase risk of HIV transmission dramatically. Chancroid is not a lethal disease and does not cause systemic infection, not even in individuals with HIV infection. Even if left untreated, the genital lesion resolves spontaneously within 1-3 months. However, untreated infection can lead to development of painful inguinal lymphadenopathy, which can ulcerate to form buboes in 25% of cases. Left untreated, suppurative bubo formation occurs, which can progress to spontaneous rupture with formation of a deep non healing inguinal ulcer. March 18th 2021 [Dermatology - Prof. S. Iurassich] MUCOSAL CUTANEOUS REACTIONS Etiology Genetic predisposition: ● HLA A33, B15, DR53, DQ3. Etiology known in 50% cases: ● labial herpes simplex. ● mycoplasma (lung). ● drugs. ● streptococcal (tonsillitis, laryngitis). ● autoimmune diseases. ● deep fungal infections. Viral infections: ● herpes simplex. 50 ● herpes zoster. ● varicella. ● flu. ● mononucleosis. ● hepatitis B. Systemic disease: ● connectivity (SLE). ● sarcoidosis. ● inflammatory colitis. ● lymphoma. ● malignancy. Microbial infections: ● mycoplasma pneumoniae. ● histoplasma capsulatum. ● tuberculosis. ● leprosy. Drugs: ● antipyretic. ● anti-inflammatory. ● antibiotics (sulfonamides, penicillin, cephalosporins). ● barbiturates. ● antiepileptic. ● estrogens. ● vaccines (diphtheria, tetanus, polio, tbc). Endocrine factors: ● menstruation. ● pregnancy. ● UV radiation. ● ionizing radiation. ● idiopathic. Reaction Type REACTION TYPE LESIONS (SKIN, GLANDS, HAIR, NAILS) Toxic Drug embolization; necrosis by infiltration; carbon monoxide poisoning. I (antigen-antibody) Macular rash; urticaria. II (cytotoxic) Thrombocytopenic purpura. III (immuno-complex) Vasculitis; serum sickness; hemorrhagic bullous rash. IV (cell-mediated) A. Contact dermatitis. 51 ● burning. Skin signs → Typical coccardius lesions: three concentric rings = erythema, papules and vesicles. ● Peripheral erythematous band with net margins. ● Intermediate edematous ring detected, pale. ● Centrer: necrotic or vesicular, purple or hemorrhagic. Atypical macular lesions: dark-red color, central bubble vesicle. The eruption is polymorphous (many forms), hence the ‘multiforme’ in the name. Lesions may be at various stages of development with both typical and atypical targets present at the same time. A full skin examination may be required to find typical targets, as these may be few in number. Infections. Infections are probably associated with at least 90% of cases of erythema multiforme. The single most common trigger for developing erythema multiforme is herpes simplex virus (HSV) infection, usually herpes labialis (cold sore on the lip) and less often genital herpes. HSV type 1 is more commonly associated than type 2. The herpes infection usually precedes the skin eruption by 3–14 days. Mycoplasma pneumonia (a lung infection caused by the bacteria Mycoplasma pneumoniae) is the next most common trigger. Many different virus infections have been reported to trigger erythema multiforme including: ● Parapoxvirus (orf and milkers' nodules). ● Herpes varicella-zoster (chickenpox, shingles). 54 ● Adenovirus. ● Hepatitis viruses. ● Human immunodeficiency virus (HIV). Dermatophyte fungal infections (tinea) have also been reported in association with erythema multiforme. Typically in erythema multiforme, few to hundreds of skin lesions erupt within a 24-hour period. The lesions are first seen on the backs of hands and/or tops of feet and then spread down the limbs towards the trunk. The upper limbs are more commonly affected than the lower. Palms and soles may be involved. The face, neck and trunk are common sites. Skin lesions are often grouped on elbows and knees. There may be an associated mild itch or burning sensation. The initial lesions are sharply demarcated, round, red/pink and flat (macules), which become raised (papules/palpable) and gradually enlarge to form plaques (flat raised patches) up to several centimeters in diameter. The center of the papule/plaque darkens in colour and develops surface (epidermal) changes such as blistering or crusting. Lesions usually evolve over 72 hours. The typical target lesion (also called iris lesion or coccardius) of erythema multiforme has a sharp margin, regular round shape and three concentric color zones: ● The center is dusky or dark red with a blister or crust ● Next ring is a paler pink and is raised due to oedema (fluid swelling) ● The outermost ring is bright red. Atypical target lesions show just two zones and/or an indistinct border. The eruption is polymorphous (many forms), hence the ‘multiforme’ in the name. Lesions may be at various stages of development with both typical and atypical targets present at the same time. A full skin examination may be required to find typical targets, as these may be few in number. There is no associated swelling of face, hands or feet, despite these being common sites of rash distribution. However, the lips are often swollen, especially in erythema multiforme major. PE minus Only one oral mucosa is involved. PE major Multiple mucosa involvement. Stevens Johnson Syndrome Mucositic lesions from drugs. Mucosal lesions, if present, typically develop a few days after the skin rash begins. In erythema multiforme minor, mucous membrane involvement is absent or mild. Mucosal changes, if present, consist initially of redness of the lips and inside the cheek. Sometimes blisters develop and quickly break to form erosions and ulcers. In erythema multiforme major, one or more mucous membranes are typically affected, most often the oral mucosa: ● Most commonly lips, inside the cheeks, tongue. 55 ● Less commonly the floor of the mouth, palate, gums. Mucosal lesions consist of swelling and redness with blister formation. The blisters break quickly to leave large, shallow, irregular shaped, painful ulcers that are covered by a whitish pseudomembrane. Typically the lips are swollen with hemorrhagic crusts. The patient may have difficulty speaking or swallowing due to pain. With mycoplasma pneumonia, the mucous membranes may be the only affected sites (mucositis). This can be severe and require hospitalisation due to difficulty eating and drinking. Whether this is a limited form of erythema multiforme has not been determined. It is also known as Fuchs syndrome, and mucosal erythema multiforme may occasionally be due to recurrent herpes simplex. Polymorphic Erythema Minor In erythema multiforme minor, mucous membrane involvement is absent or mild. Mucosal changes, if present, consist initially of redness of the lips and inside the cheek. Sometimes blisters develop and quickly break to form erosions and ulcers. Affects less than 10% of the body. Objective signs, skin lesions → ● Typical: bubbles on cockade (skin, mucous). ● Atypical: two rings (peripheral edema, depressed central disk). Clinical mucous signs → ● Ulcers (multiple ulcers lead to crusts). ● Hemorrhagic erosion. ● Burning, pain, dysphagia. ● Oral mucosa: aphthosis, crusts in the border of the lips, back of the tongue, soft palate, posterior oral cavity, vestibule. ● Pharynx, larynx, esophagus, nasal cavity. ● Eye: conjunctivitis, blepharitis, iritis, uveitis. ● Fuchs syndrome (oral ocular lesions). ● Anogenital (cockade like lesions); perianal, penile, scrotal, labial. Polymorphic Erythema Major ● Multiple mucosal involvement. ● Affects more than 10% of the body. Stevens-Johnson Syndrome (SJS) ● Toxic epidermal necrolysis (Lyell syndrome, TEN). ● Macule form. ● Widespread erythema form. Stevens-Johnson syndrome (SJS) is a serious systemic disorder of the skin and mucous membranes that affects between 10 to 30% of the body and is also associated with respiratory illnesses. 56 LICHEN PLANUS Disease of the skin and/or mucous membranes; unknown cause and there is no cure (we control symptoms). It may be found with other diseases of altered immunity, such as ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosus, and myasthenia gravis. Lichen planus has been described as an: ● Papulosquamous disorder. ● Mucocutaneous disease. ● Inflammatory disease. The cause of lichen planus is unknown. The term lichenoid reaction refers to a lesion of similar histopathologic and clinical appearance to lichen planus. A lichenoid reaction may be due to: ● Drugs (gold salts, beta blockers, diuretics, antimalarials, penicillamine, thiazide, furosemide, spironolactone, metformin). ● Amalgam (metal alloys), fillings, dental materials. ● Graft-versus-host disease (on the palms, soles, face, upper trunk) ● Hepatitis B and C, cirrhosis. ● Stress (Grinspan's syndrome). Lichen planus affects: ● cutaneous surfaces (skin, scalp, nails). ● mucosal surfaces. Skin lesions Papules: ● violaceous. ● with white lines (Wickham’s striae). ● poligonal. ● grouped, linear, anular (papules often arise after isomorphic phenomenon). ● the papules are often itchy. 6 Ps of LP ● Papules ● Plaques ● Purple ● Polygonal ● Planar (flat-topped) ● Pruritic Papules (end points): ● Purple ● Itchy ● Wickham’s striae (white lines) 59 On black skin the inflammatory process makes the lesions darker (dark purple, almost blue). Skin lesion: distributed papules (skin, scalp, nail). ● neck, scalp. ● arms, wrists (flexor area). ● palms, soles, dorsal hands. ● intertriginous areas (inverse lichen planus). Scalp Lichen Planus (alopecia) ● also known as lichen planopilaris or follicular. ● it can cause scarring alopecia. Produces inflammation of hair follicles and gradual replacement with scarring. Nail LP: destruction of the nail fold and bed. ● Ridging of the nail plate. ● Thinning of the nail plate. ● Atrophy of the nail bed. Skin different forms: ● Anular → ring-shaped lesions; circular groups of papules with unaffected skin in the center. ● Linear → papules are arranged in a line; may be secondary to trauma (isomorphic phenomenon); Koebner’s sign. ● Hypertrophic/Lichen planus verrucosus → it occurs on the extremities (shins, interphalangeal joints). ● Atrophic → white papules or plaques with central superficial atrophy. ● Bullous → vesiculobullous lichen planus; development of vesicles and bullae. ● Ulcerative → painful bullae and ulceration. ● Pigmented → dark brown macules. Mucous Membranes Forms (LPMM) Mucous membranes: papules are milky white and have a white lacework on the buccal mucosa. LPMM may have one lesion or be multifocal. It includes: ● esophageal lichen planus; ● oral mucosal lichen planus; ● genital lichen planus. Esophageal LP (esophageal mucosa) → esophageal inflammation, development of an esophageal stricture. Oral LP → ● bilaterally; ● white lesions on the inner cheek, tongue, lips, gingivae, floor of the mouth, palate; ● burning to severe pain. [tongue pic with two colors: yellow is candida and white is lp] 60 Oral forms: ● Reticular → net-like or spider web-like appearance, white lines - oral variants of Wickham’s striae. ● Papular (white papules) → you do not see the reticular web-like form, only white papules that are consistent. ● Plaque-like (white patch) → very clear white patch that resembles leukoplakia. If we see only these lesions we may think it is leukoplakia, but if you see other similar lesions on the skin it may be LP. However, perform a biopsy. ● Atrophic oral LP → atrophic, desquamative gingivitis. They do not grow; very superficial. ● Bullous. ● Erosive/ulcerative → from burning to severe pain; oral ulcers with persistent areas of redness. Inflammatory process. White lines are present in most oral lesions. Lichen Sclerosus et Atrophicus Genitalis Lichen sclerosus is an uncommon but distinctive chronic cutaneous disease. Autoimmune inflammatory process. ● Cases in females outnumber those in males by 10:1. ● 15% of patients know of a family member with lichen sclerosus. ● It may follow or co-exist with another skin condition, most often lichen simplex, psoriasis, erosive lichen planus, vitiligo or morphea. ● People with lichen sclerosus often have a personal or family history of another autoimmune disease such as thyroid disease (about 20% of patients), pernicious anaemia, or alopecia areata. At a glance, LS may be confused with guttate morphea, lichen planus, or discoid lupus erythematosus. The difference: 61 [Dermatology - Prof. Stefano Iurassich] PSORIASIS Psoriasis is a chronic inflammatory skin condition characterized by clearly defined and scaly silvery plaques (thickened skin). The primary lesion is a well-demarcated erythematous plaque (inferiorly) with a silvery scale (superiorly). The disease is transmitted genetically, with at least 10% of people inheriting one or more genes that may lead to psoriasis. A family history of psoriasis predicts an early age of onset. The disease is lifelong and characterized by chronic, recurrent exacerbations and remissions that are emotionally and physically debilitating. ● Chronic. ● Relapsing. ● Immune-mediated disease. ● 2-4% of the general population. HLA: B13, B16, B17, B37, DR7, CW6. Diagnosis End Points The diagnosis is made by analyzing the skin lesion, and the presence of Arthritis in some particular cases and also Pruritus, especially in the psychosomatic type. ● Skin lesions. ● Arthritis – particular cases. ● Pruritus in psychosomatic type. Skin lesions present erythematosus patches, silvery scaly patches, pustules (without microbes), and itching. They begin as red, scaling papules that coalesce to form round to oval plaques, which can easily be distinguished from the surrounding normal skin. The scale is adherent and silvery white, and reveals bleeding points when removed (Auspitz sign). Scale may become extremely dense, especially on the scalp. In intertriginous areas, like in the intergluteal fold, it is common to have macerated scales, due to the friction between the skin. The deep, rich red color is another characteristic feature and remains constant in all areas. Chronic papules and plaques are present at sites of repeated trauma. Clinical Types ● Vulgaris: ○ Plaque like. ○ Palmoplantaris. ○ Guttate. ○ Inverse. ● Napkin. 64 ● Pustular. ● Erythrodermic. ● Oral psoriasis. ● Seborrheic like psoriasis. ● Psoriatic arthritis. Psoriasis Vulgaris Plaque Like → ● Most common form. ● Affects 85-90% of people with psoriasis. ● Inflamed skin covered with silvery scales. ● Reddish papules surmounted by scales. ● They progress to patches or plaques. ● It occurs on elbows, knees, scalp, palms, soles, genitals, back. Psoriasis Vulgaris Palmoplantaris → ● Erythematous scaly patches. ● Edges are defined. ● Present on palms and soles. ● Very dry skin that causes linear ruptures. ● Differentiated from eczema due to the lack of vesicles and crusts. Psoriasis Vulgaris Guttate Type → ● Numerous, teardrop-shaped erythematous, scaly plaques. ● Occurs after a streptococcal infection (pharyngitis). Psoriasis Vulgaris Inverse (Inversa) → ● Smooth, inflamed patches that affect skin fold. ● Can affect groins, genitals (vulva), inflammatory folds (intergluteal, armpits, breasts, overweight abdomen). Napkin Psoriasis → ● Common in infants. ● Red papules with silver scale in the diaper area. Pustular Psoriasis → ● Sterile pustules. ● Can be generalized (on any part of the body) or localized to the hands and feet (palmoplantar pustulosis). General pustular psoriasis includes: ● Pustular psoriasis of von Zumbusch, a rare and severe form that may require hospitalization that presents with generalized eruption, fever, leukocytosis, muscle aches and nausea, as well as acute erythema and numerous sterile pustules. The disorder may be caused by irritating topical, infection, pregnancy, drugs, hypocalcemia, suspension of the steroid therapy. ● Annular pustular psoriasis (APP) is a rare form usually present in childhood. Characterized by ring-shaped plaques with pustules and yellow crust. 65 Localized pustular psoriasis includes: ● Acrodermatitis continua, limited to the fingers and toes but may spread to the hands and feet. ● Pustulosis palmaris et plantaris, which is a chronic disorder with sterile pustules that develop within areas of erythema on the palms and soles. Pustules are scaly, red and erupting. Psoriatic Erythroderma → ● Widespread inflammation and exfoliation of the skin. ● Severe itching, swelling and pain. This form can be fatal. The extreme inflammation and exfoliation disrupt the body's ability to regulate temperature. Oral Psoriasis → ● Rare. ● Involves the lining of the mouth. ● White or gray-yellow plaques. ● Fissured tongue. Seborrheic-like Psoriasis → ● It shows clinical aspects of psoriasis and seborrheic dermatitis. ● Red plaques with greasy scales. ● Present in areas of sebum production (scalp, forehead, nose, mouth, chest). Psoriatic Arthritis (PA) → ● Chronic inflammatory arthritis. ● Association with skin and nail psoriasis. ● Tissue type HLA-B27. ● No rheumatoid factor in the serum (seronegative). ● Painful inflammation of the joints. ● Commonly affects the joints of fingers and toes. The fingers and toes are “sausage-shaped” (dactylitis); joints are red and warm. There is pain, swelling and stiffness. Hand joints involved: proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrist. Types of psoriatic arthritis include: ● Asymmetric → affects 70% of patients, does not occur on both sides of the body. ● Symmetric → symmetrical seronegative arthritis, 25% of cases, affects joints on both sides of the body. ● Mutilans → affects 5% of patients; severe, deforming, destructive arthritis. ● Sacroiliitis/Spondylitis → stiffness of the spine or neck; can affect hands and feet. ● Distal interphalangeal → found in 5% of patients; inflammation and stiffness in the joints of the fingers and toes. Diagnosis of psoriatic arthritis involves family history of psoriasis, negative test result for rheumatoid factor, joints ultrasound (hook appearance, distal bony heads with awl appearance). 66 ● Atrophy of the epidermis. ● Incontinence of pigment. ● Inflammatory cell infiltrate (usually lymphocytic) in perivascular, periappendageal and subepidermal locations. ● Abundance of mucin is seen within the dermis. The histopathologic features differ depending on the type and age of the lesion. Workup Only patients with systemic lupus erythematosus (SLE) have a positive lupus band test (LBT), defined as the presence of multiple immune reactants in the basement membrane zone. The LBT is neither sensitive nor specific and has mostly been reported by advances in serologic testing. Screening for SLE should occur upon diagnosis of DLE using history and physical examination, as well as laboratory screening including complete blood cell count, renal function tests and urinalysis. Elevated sedimentation rate (VES) may occur, as well as positive rheumatoid factor and decreased complement levels. Abnormal renal function tests and/or urinalysis with proteinuria may reflect the presence of renal involvement. 20% of DLE patients manifest a positive ANA test (antinuclear antibodies). Anti-Ro (SS-A) autoantibodies are present in approximately 1-3% of patients. Antinative deoxyribonucleic acid (DNA) or anti-Sm antibodies usually reflect SLE, and they may occur in some patients (<5%). Approach Screening for systemic lupus erythematosus (SLE) should occur upon diagnosis of discoid lupus erythematosus (DLE) using history and physical examination, as well as standard laboratory screening including complete blood cell count, renal function tests, and urinalysis. Treatment Therapy begins with the use of sun-protective measures. Standard medical therapy includes topical or intralesional corticosteroids and antimalarials. The latter seems to lessen progression to SLE and to lower the risk of thrombovascular disease. Topical calcineurin inhibitors (tacrolimus) and topical retinoids have also been used. Systemic corticosteroids are avoided (due to substantial adverse effects). Thus, for recalcitrant disease, including methotrexate, mycophenolate mofetil, azathioprine and thalidomide should be considered. Hydroxychloroquine is the first-line systemic agent for DLE, whereas chloroquine is second-line. Antimalarials have been considered to be less effective in patients who smoke; however, it is also possible that DLE in these patients was worse. 69 Ocular toxicity is a well-known risk as both hydroxychloroquine and chloroquine can deposit in the retina with subsequent irreversible retinopathy. Baseline ocular examinations prior to therapy initiation and then annual examinations for 5 years of therapy, as ocular toxicity is a cumulative effect. Morphea Morphea (localized scleroderma) is characterized by excessive collagen deposition leading to thickening of the dermis and/or subcutaneous tissues. It is classified into circumscribed, generalized, linear and pansclerotic subtypes (more deep). It can be present with extracutaneous manifestations but not with features of systemic sclerosis (sclerodactyly, Raynaud, nailfold and capillary changes, and progressive internal involvement). Lab abnormalities may be found: eosinophilia, polyclonal hypergammaglobulinemia and positive ANA. 1-6% of patients progress to systemic sclerosis. However, these patients may have been initially misclassified. Pathophysiology Overproduction of collagen, particularly types I and III collagen, by fibroblasts in affected tissues. Common in all forms of morphea, although the mechanism by which these fibroblasts are activated is unknown. Proposed factors involved in the pathogenesis of morphea include endothelial cell injury, immunologic (T lymphocyte) and inflammatory activation) and dysregulation of collagen production. An autoimmune component is supported by the frequent presence of autoantibodies in affected individuals, as well as the association of morphea with other autoimmune diseases, including systemic lupus erythematosus, vitiligo, type 1 diabetes and autoimmune thyroiditis. Two thirds of adults with morphea present with plaque/superficial circumscribed lesions, with generalized, linear and deep variants each accounting for approximately 10% of cases. Up to half of cases of morphea occur in pediatric patients. In this group, linear morphea predominates (two thirds of cases), followed by the plaque/superficial circumscribed (25%) and generalized (5%) subtypes. Of note, as many as half of the patients with linear morphea have coexisten plaque-type lesions. Typically benign, self-limited course. However, linear and deep morphea subtypes can cause considerable morbidity, especially in children, when they interfere in growth. Joint contractures, limb-length discrepancy and prominent facial atrophy result in substantial disability and deformity in a quarter to half of all patients with linear or deep morphea. 70 Neurologic and ophthalmologic manifestations can also occur in those with craniofacial lesions; such complications are more common in pediatric cases. Although morphea occurs in persons of all races, it appears to be more common in whites, who comprise 73-82% of patients seen. Women are affected approximately 3 times as often as men for all forms of morphea, except the linear subtype which has a slight female predominance. Genital lichen sclerosus has been reported with high frequency in patients with morphea. Extracutaneous involvement is present in 20% of patients and is more common in the linear and generalized subtypes. Malaise, fatigue, myalgias and arthralgias are common extracutaneous symptoms. Arthralgias are usually localized to an affected extremity. Linear and deep lesions can also be associated with arthritis, carpal tunnel syndrome and other peripheral neuropathies. Dysphagia, dyspnea and vascular complaints are also reported. Neurologic manifestations, which are more common in patients with en coup de sabre or progressive hemifacial atrophy, include seizures, headaches, cranial nerve palsies, trigeminal neuralgia, hemiparesis/muscle weakness, eye pain and visual changes. Dry eyes are also frequently reported due to eyelid or lacrimal gland sclerosis. Circumscribed morphea (morphea en plaque) is the most common subtype. There are fewer than 3 discrete lesions, predominantly on the trunk. In the superficial variant, lesions are indurated plaques 1 cm to more than 20 cm in diameter. These are primarily involving the dermis. They often begin as oval erythematous-violaceous patches or slightly edematous plaque. A lilac ring may surround the intruded region. With progression, sclerosis develops centrally while peripherally expanding. Over a period of months to years, the surface becomes smooth, shiny and ivory in color, with loss of hair follicles and sweat glands. Hyperpigmentation often ensues as lesions evolve and eventually involute. Atrophoderma of Pasini and Pierini is thought to represent a superficial form of morphea. It is typically located on the trunk and is characterized with well-defined “cliff-drop” borders and no obvious induration. Similar hyperpigmented patches with minimal induration are seen in persons with superficial morphea, which, unlike atrophoderma of Pasini and Pierini, is characterized histologically by sclerosis of the upper dermis. 71 ● As the disease progresses, the capillaries are destroyed and the muscles undergo microinfarction. ● The pathogenesis of the cutaneous component is poorly understood. Etiology The cause is unknown but the following factors have been implicated: ● A genetic component may predispose to dermatomyositis. Polymorphisms of tumor necrosis factor may be involved. ● Immunologic abnormalities are common in patients with dermatomyositis. Patients frequently have circulating autoantibodies. Abnormal T cell activity may be involved. ● Infectious agents, including viruses and Toxoplasma and Borrelia species have been suggested as possible triggers. ● Drug-induced cases have been reported. ● Associated with malignancy in several cases. Prognosis Most patients with dermatomyositis survive, in which case they may develop residual weakness and disability. Children with severe dermatomyositis may develop contractures. The disease may spontaneously remit in as many as 20% of affected patients. About 5% of patients have a fulminant progressive course with eventual death. Dermatomyositis may cause death because of muscle weakness or cardiopulmonary involvement. Patients with an associated malignancy may die of the malignancy. Amyopathic dermatomyositis is a benign form affecting the skin only. Persons with dermatomyositis often present with skin disease as one of the initial manifestations, and may be the sole manifestation at onset in 40% of individuals with this condition. Cutaneous involvement may manifest as follows: ● Eruption on exposed surfaces. ● Pruritus of skin lesions. ● Scaly scalp or diffuse hair loss. Muscle disease may occur concurrently, may precede the skin disease or may follow the skin disease by weeks to years. Muscle involvement manifests as: ● Proximal muscle weakness. ● Muscle fatigue/weakness when climbing stairs, walking, rising from a seated position, combing hair, or reaching for items above shoulders. ● Muscle pain may occur but is not a regular feature of dermatomyositis. Systemic manifestations: ● Arthralgia, arthritis. ● Dyspnea. ● Dysphagia. 74 ● Arrhythmia. ● Dysphonia. ● Malignancy, particularly in older patients. Children also commonly develop a tiptoe walking secondary to flexion contracture of the ankles in early childhood and may have extramuscular manifestations, such as the following: ● General systemic disturbances, fever, arthralgia, malaise, weight loss, Raynaud phenomenon. ● Dysphagia, similar to that of scleroderma. ● Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies. ● Gastrointestinal ulcers and infections. ● Contracture of joints. ● Pulmonary involvement due to weakness of thoracic muscles, interstitial lung disease. ● Subcutaneous calcification. Diagnosis Examination for cutaneous dermatomyositis may reveal the following findings: ● Pathognomonic cutaneous features → heliotrope (violaceous) discoloration on the upper eyelids, Gottron papules. ● Characteristic but not pathognomonic features → Malar erythema; poikiloderma in a photosensitive distribution; violaceous erythema on the extensor surfaces; periungual and cuticular changes; flat, red rash involving the face and upper trunk or other body surfaces, including knees, elbows, neck, anterior chest or back and shoulders. Laboratory and other studies that may be helpful: ● Muscle enzyme levels (creatine kinase, aldolase, aspartate aminotransferase, lactic dehydrogenase). ● Myositis-specific antibodies (rarely used). ● Antinuclear antibody levels. ● Pulmonary function studies. ● Electrocardiography. Imaging studies used in the evaluation of the disease: ● MRI. ● Chest radiography. ● Barium swallow. ● Ultrasonography of the muscles. ● Electromyography. ● CT scanning. Procedures that may be helpful: ● Skin biopsy (interface dermatitis). ● Muscle biopsy (open or via a needle); findings can be diagnostic (perivascular and interfascicular inflammatory infiltrates with adjoining groups of muscle fiber degeneration/regeneration). ● Esophageal manometry. 75 Management Therapy for the muscle component involves use of corticosteroids, with or without an immunosuppressive agent. The skin disease is treated with sunscreens, topical corticosteroids, antimalarial agents, methotrexate, mycophenolate mofetil or immunoglobulin. Medications used in dermatomyositis: ● Corticosteroids (prednisone, first-line therapy). ● Immunosuppressive agents (methotrexate, azathioprine, rituximab). ● Immune globulins. ● Calcium channel blockers. ● Antimalarial agents. PEMPHIGUS It is a disease of the skin and mucous membranes. ● Serious, acute or chronic. ● Bullous. ● Autoimmune. Inducing factors: ● Drugs. ● Virus. ● Neoplasm. ● Chemicals. Pathogenesis IgG against desmogleins (DSG) induces loss of cohesion among cells (acantholysis), producing cracks and intraepithelial bubbles due to serum influx. Acantholysis is the immunological disruption of the connections between keratinocytes (desmosomal attachments); this produces intraepidermal humid lesions. Desmogleins are a family of cadherins (DSG1, DSG3) proteins and play a role in the formation of desmosomes. Autoantibodies react against desmoglein, cells become separated from each other → acantholysis → blisters (sores). Antibodies anti-desmogleins are present in the lesion (DIF) and in the serum (IIF). Acantholysis occurs in: ● Granular layer (high or subcorneal acantholysis) for anti-DSG1 (skin). ● Basal layer (low or suprabasal acantholysis) for anti-DSG3 (skin and mucous). High acantholysis: ● Foliaceus. ● Erythematous. Low acantholysis: ● Vulgaris. 76 PEMPHIGOID ● It is a group of rare autoimmune blistering skin disease. ● It does not feature acantholysis. Types: ● Bullous pemphigoid → rarely affects the mouth. ● Mucous membrane pemphigoid → cicatricial pemphigoid (CP); no skin involvement, affects persons >60 yo. ● Gestational pemphigoid → herpes gestationis; during second or third trimester of pregnancy. Bullous Pemphigoid → ● Chronic bullous dysimmune disease. ● It affects skin and mucous membranes. Epidemiology: ● Age > 60 years. ● Paraneoplastic syndrome (carcinoma). Inducing factors: ● Drugs. ● Physical agents. ● Visceral neoplasms. Pathogenesis: IgG against the junctional zone (basal membrane). Dermal-epidermal detachment in the basal membrane (lamina lucida). Antibodies against the basal membrane are present in the serum (IIF) and in the lesion (DIF). They recognize two self-antigens into the basal cell: ● BPAG1 → cytoplasmic protein (plachine’s family) localized into the emidesmosomical plaque. ● BPAG2 → transmembrane protein. Initial phase of the disease → “urticarial patchy”; erythema and wheal lesions; round; itchy. Overt phase of the disease → “bullous”; bubbles are tense, serous/hemorrhagic on erythematous skin; involvement of the mucous membranes. Diagnosis: ● Clinic → urticarial lesions with bubbles. ● Histological → bubble dermo-epidermal. ● DIF → deposits IgG and C3 on the basal membrane (perilesional skin). ● IFI → deposits of IgG on the basal membrane (esophageal of monkey). Cicatricial Pemphigoid → Disease of the skin and mucous membranes. 79 ● Serious, acute or chronic. ● Bullous lesions, scars. ● Autoimmune. ● Conjunctival and oral mucosa affected; rarely on the skin. Pathogenesis: ● Similar to bullous pemphigoid. ● It involves the basal membrane (lamina densa). ● Bubbles hesitate in bridles and synechiae (simblefaron). ● Conjunctivitis, photophobia, blindness. ● Desquamative gingivitis. ● Bubbles result in atrophic scarring. Diagnosis: ● DIF + (as in bullous pemphigoid). ● IIF - Gestational Pemphigoid → ● Similar to bullous pemphigoid. ● Occurs in pregnant women with genetic predisposition (DR 3,4) and fertilized by partners DR2+. Incompatibility between maternal and fetal HLA leads to immune reaction against maternal skin. Clinic presentation: ● Abdomen > root of the limbs. ● Exacerbation in postpartum. ● Spontaneous resolution. IFD → IgG and C3 on the basal membrane. IFI → IgG on the basal membrane (esophageal in monkey). Differential Diagnosis: Pemphigus vs. Pemphigoid PEMPHIGUS PEMPHIGOID ● High acantholysis → pemphigus foliaceus, pemphigus erythematosus. ● Low acantholysis → pemphigus vulgaris, pemphigus vegetans. ● Bullous pemphigoid. ● Mucous membrane pemphigoid. ● Gestational pemphigoid. ● Blisters on the undamaged skin. ● Erythema and wheal lesions. ● Acantholysis. ● Dermal-epidermal detachment. ● DIF and IIF or ELISA → DSG1, DSG2. ● PBAG1, PBAG2. DERMATITIS HERPETIFORMIS - DUHRING’S DISEASE 80 ● Appearance similar to herpes. ● Chronic dermatosis associated with jejunal villous atrophy, gluten sensitive enteropathy, HLA antigens (B8, DR3, DQ2). ● Rare chronic disease. ● 15-40 years old. ● Intense itching or burning eruption (felt before the blisters appear). ● Chronic papulovesicular eruptions. ● Lesions are symmetrical. The severity is in the response to the amount of gluten ingested, and symptoms disappear if gluten ingestion is avoided. Skin symptoms may be accompanied by symptoms of celiac disease (abdominal pain, bloating, fatigue). Types: ● Erythematous. ● Papular. ● Vesicular. ● Bullous. Symptoms ● First signs → itching and burning. ● First visible signs → papules, vesicles. Involves buttocks, neck, scalp, elbows, knees, back, hairline, groin, face, shoulders, lower end of the spinal column, mouth. Three stages: 1. Skin discoloration. 2. Vesicles, papules (groups). 3. Healing by a change in the skin color. Intense itching → scratch → crusts. Complications ● Celiac disease. ● Osteoporosis. ● Intestinal lymphoma. Risk of complications decreases with a gluten-free diet. The disease has been associated with: ● Auto-immune thyroid disease. ● Insulin dependent diabetes. ● Lupus erythematous. ● Sjogren’s syndrome. ● Sarcoidosis. ● Vitiligo. 81 Neutrophils produce pus in the dermal papillae, generating characteristic blisters. IL-31 accumulation at the blisters may intensify itching. Memory B and T cells may become activated in the absence of PAMPs and DAMPs during successive encounters with tTG-modified gliadin complexes or modified gliadin alone, respectively. DIAGNOSTIC METHODOLOGY The specialist’s visit to go on from 15 to 20 minutes, sometimes up to 30’. 1. Get the patient. 2. Hypothesize diagnosis. 3. Suggest therapy. 4. Greet the patient. To get the patient: ● The patient enters and we make him sit. ● Smile and make him reassured. ● Ask what the problem is. ● If the patient is a child try to speak directly with him. ● Postpone the discussion on previous visits and therapies, but at the same time I welcome all the cards he brings me. To observe the patient (diagnosis): ● Behavior. ● Attitude (defensive, etcc). ● Posture (static and dynamic). ● Family history. ● Finally observe the lesions and look for the primary lesion. 2-3 minutes Objective symptoms: ● Look for the largest lesion. ● Identify it as a primary or secondary lesion. ● Deduce the primary lesion. ● Observe if it is a single lesion or lesions are superimposed. Describe the lesion for: ● Onset (on erythematous skin or not). ● Geometric shape. ● Color (specific or if it expresses the content). ● Surface (smooth, umbilicated, vegetating, ulcerated). ● Base (wide, pedunculated). ● Margin (net or shaded). ● Site of the lesion → somatic (body region); topographical (follicular, hairless skin, acral, photo exposed, seborrheic regions, covered areas, folds, hairy regions). ● Arrangement (single, grouped). 84 ● Distribution (symmetric, asymmetric). Subjective symptoms: ● Paresthesia. ● Itch. ● Burning. ● Pain. Evolutive history of the disease: ● Recurrent, seasonal. ● If it increases with cold and/or heat. ● Post traumatic lesion. ● State of evolution (acute, chronic). ● Age and sex of the patient. Look for characteristic signs by visual score: ● Red or white dermographism. ● Koebner (reactive isomorphism) → after an injury the skin produces the lesion which is genetically determined. ● Nikolsky → enlargement of the bullous lesion after trauma. ● Beighton test → evaluates joint mobility. ● Wood lamp → skin changes color. FIRST STEP: ● Search the common lesions. ● Identify initial (primitive) lesion. ● Observe color, surface, base, margin. SECOND STEP: ● Placement (above and under). ● Arrangement (single, multiple). ● Distribution (symmetrical or asymmetrical). THIRD STEP: ● Side (covered, exposed, photo exposed, extremity, hair, hairless, follicular, mucous membranes, skin). ● Sex and age. DISEASE LESIONS Eczema Erythema, vesicles. Psoriasis Erythema, scales. Lichen Erythema, papules. Pemphigus Bullae. 85 Pemphigoid Erythema, vesicles, bullae. Common eczema lesion → erythema (widespread red color), associated vesicles which are humid lesions because they have a liquid filling. Vesicles have a roof and a floor. Skin Diseases ● Acne = comedone (small flesh-colored acne papules) → other. ● Eczema = erythema → crust + scale. ● Psoriasis = erythema + scales. ● Tinea = erythema + scales. ● Candida = exudative → scale (disepithelization). Acne ● Comedone → closed = skin color, open = black. ● Papule. ● Pustule → crust. ● Cysti. ● Scar (keloid or hypertrophic; ice pick or dystrophic scar). ● Conglobate (all lesions). Pruritus Unpleasant sensation that provokes the desire to scratch. Itch ranges in intensity from a mild annoyance to an intractable, disabling condition. Certain systemic diseases have long been known to cause pruritus (reported in 10-50%of patients). Generalized pruritus may be classified into the following categories on the basis of the underlying causative disease: ● Renal pruritus. ● Cholestatic pruritus. ● Hematologic pruritus. ● Endocrine pruritus. ● Pruritus related to malignancy. ● Idiopathic generalized pruritus. Physical Examination It assists in differentiating between systemic causes of pruritus and primary dermatologic conditions. When systemic disease underlies pruritus, patients may either have normal appearing skin or skin lesions. Skin lesions in systemic disease: ● Excoriations. ● Prurigo nodules. ● Lichen simplex chronicus. ● Signs of a secondary bacterial infection. Aging 86 are most commonly involved, while, in genital HSV infection, the sacral nerve root ganglia (S2-S5) are involved. 3. Reactivation: The reactivation and replication of latent HSV, always in the area supplied by the ganglia in which latency was established, can be induced by various stimuli (eg, fever, trauma, emotional stress, sunlight, menstruation), resulting in overt or covert recurrent infection and shedding of HSV. In immunocompetent persons who are at an equal risk of acquiring HSV-1 and HSV-2 both orally and genitally, HSV-1 reactivates more frequently in the oral rather than the genital region. On the other hand, HSV-2 reactivates 8-10 times more commonly in the genital region than in the orolabial regions. Reactivation is more common and severe in immunocompromised individuals. Cellular immunity is an important defense against herpes simplex. Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals with AIDS. Herpes simplex infection can also complicate burn wounds or damaged skin such as in atopic dermatitis or other allergic dermatoses. HSV is distributed worldwide. Humans are the only natural reservoirs, and no vectors are involved in transmission. Endemicity is easily maintained in most human communities owing to latent infection, periodic reactivation, and asymptomatic virus shedding. HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare. Treatment → The antivirals ( oral, intravenous and topical) acyclovir, valacyclovir, famciclovir and pensiclovir are well established treatments for both HSV-1 and HSV-2. They all act by interfering with the viral DNA polymerase and hence, viral genome replication. Overall, medical treatment of herpes simplex virus (HSV) infection is centered around specific antiviral treatment. While the same medications are active against HSV-1 and HSV-2, the location of the lesions and the chronicity (primary or reactivation) of the infection dictate the dosage and frequency of medication. Topical treatments do not appear to be as effective as systemic medications. Antivirals are effective when taken within 72 hours of lesion appearance in genital herpes. Anticipatory treatment is also recommended in situations where decreasing viral shedding decreases the likelihood of infecting seronegative individuals with the virus. Appropriate wound care is needed, and treatment for secondary bacterial skin infections may be required. Intravenous (IV) acyclovir therapy should be provided for patients who have severe HSV disease or complications that necessitate hospitalization (e.g., disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningoencephalitis). The initiation of high-dose acyclovir therapy as early as possible in the course of the illness provides the best chance for a patient to survive with minimal neurologic damage. HSV encephalitis requires 21 days of intravenous therapy. 89 Mucosal membranes: papules ● Milky-white with white lacework on the buccal mucosa. Mucosal forms affects: ● Gastrointestinal tract → mouth, pharynx, esophagus, stomach, anus. ● Larynx, ears, nose, conjunctiva of the eyes. ● Other mucosal surfaces → genitals, bladder, peritoneum. Leukoplakia ● White patch or plaque on healthy mucosa. ● Painless, rough to the touch, not removable by rubbing. ● It may occur in any area of the oral mucosa. ● Clinical characteristics of the surface leukoplakia made it classified into different forms: uniform or plain, inhomogeneous, proliferative warty, chronic hyperplastic. Squamous Cell Carcinoma ● From precancerous lesions (actinic keratoses). ● Clinic → plaque or nodule, vegetating, ulcerated, irregular growth, infiltrated ● Lips, tongue, mouth, gums: nodule, palate: red or white plaque (keratotic) Angular Cheilitis (Labial Commissure) ● Can progress towards the inside (mucosa) → candidiasis. ● Can progress towards the outside (skin) → bacterial infection. ● Limited to the area of the labial commissure → irritative contact dermatitis (toothpaste). 90