Pemphigus PDF - A Bullous Autoimmune Disease

106 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES PEMPHIGUS ICD-9 : 694.4 ° ICD-10 : L10 ! " ! A serious, acute or chronic, bullous autoimmune -...

106 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES PEMPHIGUS ICD-9 : 694.4 ° ICD-10 : L10 ! " ! A serious, acute or chronic, bullous autoimmune - ! PV: suprabasal acantholysis. PF: subcorneal acan- - disease of skin and mucous membranes based on tholysis - acantholysis. ! IgG autoantibodies to desmogleins, transmem- ! Two major types: pemphigus vulgaris (PV) and - brane desmosomal adhesion molecules. pemphigus foliaceus (PF) - ! Serious and often fatal unless treated with im- ! PV: flaccid blisters on skin and erosions on munosuppressive agents. mucous membranes. PF: scaly and crusted skin lesions. - - CLASSIFICATION CLINICAL MANIFESTATION Two major types: pemphigus vulgaris (PV) PV usually starts in the oral mucosa, and months and pemphigus foliaceus (PF). In addition, may elapse before skin lesions occur; lesions - - - - - paraneoplastic pemphigus (PP) associated with may be localized for months, after which gener- - malignancy and# IgA pemphigus (Table 6-2). alized bullae occur. Less frequently there may be a generalized, acute eruption of bullae from the beginning. No pruritus (as occurs in pemphig- EPIDEMIOLOGY oid but burning and pain in erosions or eroded - - bullae). Painful and tender mouth lesions may PV: Rare, more common in Jews and people of - - prevent adequate food intake. Epistaxis, hoarse- Mediterranean descent. In Jerusalem the inci- - - - - ness, dysphagia. Weakness, malaise, weight loss. dence is estimated at 16 per million, whereas in - PF has no mucosal lesion and starts with scaly, France and Germany it is 1.3 per million. - - crusted lesion on an erythematous base, initially - PF: Also rare but endemic in rural areas in in seborrheic areas. - Brazil (fogo selvagem), where the prevalence can be as high as 3.4%. Skin Lesions of PV Round or oval vesicles Age of Onset 40 to 60 years; fogo selvagem - - and bullae with serous content, flaccid (flabby) also in children and young adults. (Fig. 6-9), easily ruptured, and weeping (Fig. Sex Equal incidence in males and females, but 6-10), arising on normal skin, randomly predominance of females with PF in Tunisia - scattered, discrete. Localized (e.g., to mouth or and Colombia. circumscribed skin area), or generalized with a random pattern. Extensive erosions that bleed easily (Fig. 6-11), crusts particularly on scalp. ETIOLOGY AND PATHOGENESIS An autoimmune disorder. Loss of the normal TABLE 6-2 Classification of Pemphigus - cell-to-cell adhesion in the epidermis (acan- tholysis) occurs as a result of circulating anti- - Pemphigus vulgaris Pemphigus vulgaris: localized and generalized bodies of the IgG class; these antibodies bind - = to desmogleins, transmembrane glycoproteins - Pemphigus vegetans: localized - in the desmosomes, members of the cadherin Drug-induced superfamily. In PV, desmoglein 3 (in some, - - - - Pemphigus foliaceus also desmoglein 1). All patients with PV have Pemphigus foliaceus: generalized autoantibodies to desmoglein 3. Those with - mucocutaneous PV also have antibodies to Pemphigus erythematosus: localized - Fogo selvagem: endemic - - desmoglein 1; those with only mucosal involve- - - - - ment, only to desmoglein 3. In contrast, PF Drug-induced - patients have autoantibodies only to desmo- -- Paraneoplastic pemphigus: associated with malignancy glein 1. These autoantibodies interfere with IgA pemphigus: subcorneal pustular dermatosis and calcium-sensitive adhesion function and thus intraepidermal neutrophilic IgA dermatitis induce acantholysis (Image 6-2). -  SECTION 6 BULLOUS DISEASES 107 FIGURE 6-9 Pemphigus vulgaris This is the classic initial lesion: flaccid, easily ruptured vesicle or bulla on normal-appearing skin. Ruptured vesicles lead to erosions that subsequently crust. IMAGE 6-2 Desmoglein compensation Triangles represent the distribution of Dsg 1 and 3 in skin and mucous membranes. Anti-Dsg 1 antibodies in pemphigus foliaceus cause acantholysis only in the superficial epi- dermis of skin. In the deep epidermis and in mucous membranes, Dsg 3 compensates for antibody-induced loss of function of Dsg 1. In early pemphigus vulgaris, antibodies are present only against Dsg 3, which cause blisters only in the deep mucous membrane where Dsg 3 is present without compensatory Dsg 1. However, in muco- cutaneous pemphigus, antibodies against both Dsg 1 and Dsg 3 are present, and blisters form in both mucous membrane and skin. The blister is deep probably because antibodies diffuse from the dermis and interfere first with the function of desmosomes at the base of the epidermis. [From J Stanley, in K Wolff et al (eds): Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, McGraw-Hill, 2008, p 463.] 108 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES Since blisters rupture so easily, only erosions are Drug-Induced Pemphigus PF As in PV, associ- seen in many patients. These are very painful ated with D-penicillamine and less frequently (Fig. 6-11). by captopril and other drugs. In most, but not Nikolsky Sign Dislodging of epidermis by - all, instances the eruption resolves after termi- lateral finger pressure in the vicinity of lesions, - nation of therapy with the offending drug. which leads to an erosion. Pressure on bulla leads to lateral extension of blister. PARANEOPLASTIC PEMPHIGUS (PNP) Sites of Predilection Scalp, face, chest, axillae, - - - groin, umbilicus. In bedridden patients, there is This is a disease sui generis (see Section 18). extensive involvement of back (Fig. 6-11). Mucous membranes primarily and most se- Mucous Membranes Bullae rarely seen, ero- verely involved. Lesions combine features of sions of mouth and nose, pharynx and larynx, pemphigus vulgaris and erythema multiforme, vagina. - clinically and histologically. Skin Lesions of PF Most commonly on face, & scalp, upper chest, and abdomen. Scaly, crusted LABORATORY EXAMINATIONS = erosions on an erythematous base. In early - - or localized disease, sharply demarcated in Dermatopathology PV: Light microscopy (se- seborrheic areas; may stay localized for a long lect early small bulla or, if not present, margin time or progress to generalized disease and of larger bulla or erosion): Separation of kerati- exfoliative erythroderma. Initial lesion also nocytes, suprabasally, leading to split just above - - a flaccid bulla but this is rarely seen because of the basal cell layer and vesicles containing sepa- superficial location (see histopathology below). rated, rounded-up (acantholytic) keratinocytes. PF: Superficial form with acantholysis in the granular layer of the epidermis. VARIANTS (SEE TABLE 6-2) Immunopathology Direct immunofluores- cence (IF) staining reveals IgG and often C3 - Pemphigus Vegetans (PVeg) Usually confined deposited in lesional and paralesional skin in to intertriginous regions, perioral area, neck, the intercellular substance of the epidermis. and scalp. Granulomatous vegetating purulent Serum Autoantibodies (IgG) detected by indi- = plaques that extend centrifugally. In these pa- rect IF (IIF) or enzyme-linked immunosorbent tients there is a granulomatous response to the = assay (ELISA). Titer usually correlates with autoimmune damage of PV. activity of disease process. In PV autoantibod- Drug-Induced PV Clinically identical to spor- ies are directed against a 130-kDa glycopro- adic PV. Several different drugs implicated, most tein designated desmoglein 3 and located in significantly, captopril and D-penicillamine. desmosomes. In PF circulating autoantibodies - to a 160-kDa intercellular (cell surface) antigen, Brazilian Pemphigus (Fogo Selvagem) A desmoglein 1, in the desmosomes of keratino- distinctive form of PF endemic to south cen- - cytes. PV (130 kDa) and PF (160 kDa) antigens tral Brazil. Clinically, histologically, and immu- differ (Image 6-2). This explains the different nopathologically identical to PF. Patients sites of acantholysis and thus the different clini- improve when moved to urban areas but relapse cal appearance of the two conditions. after returning to endemic regions. It is specu- lated that the disease is somehow related to an arthropod-borne infectious agent, with cluster- DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS ing similar to that of the black fly—Similium incrimanum. More than 1000 new cases per year Can be a difficult problem if only mouth lesions are estimated to occur in the endemic regions. are present. Aphthae, mucosal lichen planus, Pemphigus Erythematosus (PE) Synonym: erythema multiforme. Differential diagnosis Senear-Usher syndrome. A localized vari- includes all forms of acquired bullous diseases ety of PF largely confined to seborrheic sites. (see Table 6-3). Biopsy of the skin and mucous Erythematous, crusted, and erosive lesions in the membrane, direct IF, and demonstration of “butterfly” area of the face, forehead, and prest- circulating autoantibodies confirm a high index ernal and interscapular regions. These patients of suspicion. have immunoglobulin and complement depos- its at the dermal-epidermal junction, in addi- COURSE tion to intercellular pemphigus antibody in the epidermis, and may have antinuclear antibodies, In most cases the disease inexorably progress- as is the case in lupus erythematosus. es to death unless treated aggressively with  SECTION 6 BULLOUS DISEASES 109 FIGURE 6-10 Pemphigus vulgaris Widespread confluent flaccid blisters on the lower back of a 40-year-old male who had a generalized eruption including scalp and mucous membranes. The eroded lesions are extremely painful. FIGURE 6-11 Pemphigus vulgaris Widespread confluent erosions that are very painful and bleed easily in a 53-year-old male. There are hardly any intact blisters because they are so fragile and break easily. The blood tracts go sideways because the patient had been lying on his right side before the photograph was taken.  110 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES immunosuppressive agents. The mortality rate agents in poorly controlled patients, in has been markedly reduced since treatment has the initial phases of treatment to reduce become available. Currently, morbidity related antibody titers. to glucocorticoids and immunosuppresive Gold therapy, for milder cases. After an initial test dose of 10 mg IM, 25–50 mg - therapies. of gold sodium thiomalate is given IM at T - MANAGEMENT weekly intervals to a maximum cumula- tive dose of 1 g. - Glucocorticoids 2 to 3 mg/kg body weight Mycophenolate mofetil (1 g twice daily) has - of prednisone until cessation of new blister been reported to be beneficial, and clini- formation and disappearance of Nikolsky sign. cal studies are ongoing. - Then rapid reduction to about half the initial High-dose intravenous immunoglobulin dose until patient is almost clear, followed by (HIVIg) (2 g/kg body weight every 3–4 very slow tapering of dose to minimal effective weeks) has been reported to have a glu- maintenance dose. cocorticoid-sparing effect. Expensive. Concomitant Immunosuppressive Therapy Immunosuppressive agents are given concomi- - Rituximab (monoclonal antibody to CD20) presumably targets B cells, the precursors tantly for their glucocorticoid-sparing effect: of (auto) antibody-producing plasma cells. Given as intravenous therapy once a Azathioprine, 2–3 mg/kg body weight until week for 4 weeks, shows dramatic effects complete clearing; tapering of dose to - in some and at least partial remission in 1 mg/kg. Azathioprine alone is contin- other patients. Serious infections may ued even after cessation of glucocorticoid be seen. treatment and may have to be continued for many months or years. Other Measures Cleansing baths, wet dress- Methotrexate, either orally (PO) or IM at ings, topical and intralesional glucocorticoids, doses of 25 to 35 mg/week. Dose adjust- antimicrobial therapy per documented bacte- ments are made as with azathioprine. rial infections. Correction of fluid and electro- Cyclophosphamide, 100–200 mg daily, with lyte imbalance. reduction to maintenance doses of 50– Monitoring Clinical, for improvement of skin lesions and development of drug-related - 100 mg/d. Alternatively, cyclophospha- mide “bolus” therapy with 1000 mg IV side effects. Laboratory monitoring of pem- once a week or every 2 weeks in the phigus antibody titers and for hematologic & initial phases, followed by 50–100 mg/d and metabolic indicators of glucocorticoid- PO as maintenance. and/or immunosuppressive-induced adverse Plasmapheresis, in conjunction with glu- effects. - cocorticoids and immunosuppressive -  SECTION 6 BULLOUS DISEASES 111 TABLE 6-3 Differential Diagnosis of Important Acquired Bullous Diseases Disease Skin Lesions Mucous Membranes Distribution PV Flaccid bullae on normal Almost always involved, Anywhere, localized or skin, erosions erosions generalized PF Crusted erosions, occasionally Rarely involved Exposed, seborrheic flaccid vesicles regions or generalized PVeg Granulating plaques, As in PV Intertriginous regions, scalp occasionally vesicles at margin Bullous Tense bullae on normal Mouth involved in Anywhere, localized or pemphigoid and erythematous 10–35% generalized skin; urticarial plaques and papules EBA Tense bullae and erosions, May be severely Traumatized regions or noninflammatory or BP-, involved (oral random DH- or LAD-like presentation esophagus, vagina) Dermatitis Grouped papules, vesicles, None Predilection sites: elbows, herpetiformis urticarial plaques, crusted knees, gluteal, sacral, and scapular areas Linear IgA Annular, grouped papules, Oral erosions and ulcers, Anywhere dermatosis vesicles, and bullae conjunctival erosions and scarring Disease Histopathology Immunopathology/Skin Serum PV Suprabasal acantholysis IgG intercellular pattern IgG AB to intercellular substance of epidermis (IIF) ELISA: AB to desmoglein 3 >> desmoglein 1 PF Acantholysis in granular IgG, intracellular pattern IgG AB to intercellular layer substance of epidermis (IIF) ELISA: AB to desmoglein 1 only PVeg Acantholysis ± intraepidermal As in PV As in PV neutrophilic abscesses, epidermal hyperplasia Bullous Subepidermal blister IgG and C3 linear at IgG AB to BMZ (IIF); pemphigoid BMZ directed to BPAG1 and BPAG2 EBA Subepidermal blister Linear IgG at BMZ IgG AB to BMZ (IIF) directed to type VII collagen (ELISA, Western blot) Dermatitis Papillary microabscesses, Granular IgA in tips of Antiendomysial herpetiformis subepidermal vesicle papillae antibodies Linear IgA Subepidermal blister Linear IgA at BMZ Low titers of IgA AB dermatosis with neutrophils against BMZ Note: AB, antibody; BMZ, basement membrane zone; BP, bullous pemphigoid; DH, dermatitis herpetiformis; EB, epidermolysis bullosa acquisita; ELISA, enzyme-linked immunosorbent assay; IIF, indirect immunofluorescence; LAD, linear IgA dermatosis; PF, pemphigus foliaceus; PV, pemphi- gus vulgaris; PVeg, pemphigus vegetans.  112 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES BULLOUS PEMPHIGOID (BP) ICD-9 : 694.5 ° ICD-10 : L12.0 ! " ➔ # ! A bullous autoimmune disease usually in elderly ! Autoantigens are keratinocyte hemidesmosome patients. proteins. - ! Pruritic papular and/or urticarial lesions with large - ! Therapy includes topical and systemic glucocorti- tense bullae. coids and other immunosuppressives. - ! Subepidermal blisters with eosinophils. - = ! C3 and IgG at epidermal basement membrane, anti- - - basement membrane IgG autoantibodies in serum. - - EPIDEMIOLOGY major - problem. Usually, however, the originally - tense bullae collapse and transform into crusts. - Age of Onset 60 to 80 years. Sites of Predilection Axillae; medial aspects of Sex A > - Equal incidence in males and females. No - thighs, groins, abdomen; flexor aspects of fore- - - - - known racial predilection. arms; lower legs (often first manifestation). - Incidence The most common bullous autoim- Mucous Membranes Practically only in the mune disease. Seven per million in Germany mouth (10–35%); less severe and painful and and France. Far more common in - - - less easily ruptured than in pemphigus. - authors’ experience in very old people. LABORATORY EXAMINATIONS ETIOLOGY AND PATHOGENESIS Dermatopathology Light Microscopy Neu- Interaction of autoantibody with bullous pem- - trophils in “Indian-file” alignment at dermal- - - - phigoid antigen [BPAG1 and BPAG2 (collagen - epidermal junction; neutrophils, eosinophils, = - - type XVII)] in hemidesmosomes of basal ke- and lymphocytes in papillary dermis; subepi- ratinocytes (Image 6-1) is followed by comple- - - dermal bulla. - - ment activation - and attraction of neutrophils- Electron Microscopy Junctional cleavage, i.e., I 61 and eosinophils. Bullous lesion results from split occurs in lamina lucida of basement mem- interaction of multiple bioactive molecules re- · > - - brane. leased from inflammatory cells. Not yet com- Immunopathology Linear IgG deposits along pletely clarified. the basement membrane zone. Also, C3, which -- may occur in the absence of IgG. CLINICAL MANIFESTATION Serum Circulating antibasement membrane IgG antibodies detected by IIF in 70% of pa- - Often starts with a prodromal eruption (ur- tients. Titers do not correlate with course of = ticarial, papular lesions) and evolves in weeks - disease. Autoantibodies in bullous pemphigoid to months to bullae that may appear sud- - recognize two types of antigens. BPAG1 is a - denly as a generalized eruption. Initially no - 230-kDa glycoprotein that has high homology - symptoms except moderate or severe pruritus; with desmoplakin I and is part of hemidesmo- - later, tenderness of eroded lesions. No constitu- somes. BPAG2 is a transmembranous 180-kDa - - tional symptoms, except in widespread, severe polypeptide (type XVII collagen). disease. - Hematology Eosinophilia (not always). - Skin Lesions Erythematous, papular or - urticarial-type lesions (Fig. 6-12) may precede DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS bullae formation by months. Bullae: large, tense, Clinical appearance, histopathology, and immu- - - - firm-topped, oval or round (Fig. 6-13); may - - - = - arise in normal, erythematous, or urticarial skin - nology permit a differentiation from other bul- lous diseases (see Table 6-3 on p 111). - - - and contain serous or hemorrhagic fluid. The - eruption may be localized or generalized, usually - scattered but also grouped in arciform and MANAGEMENT serpiginous patterns. Bullae rupture less easily - than in pemphigus, but sometimes large, bright Systemic prednisone with starting doses of = - - red, oozing, and bleeding erosions become a 50–100 mg/d continued until clear, either alone - - -  SECTION 6 BULLOUS DISEASES 113 FIGURE 6-12 Bullous pemphigoid Early lesions in a 75-year-old female. Note urticarial plaques and a small, tense blister with a clear serous content. FIGURE 6-13 Bullous pemphigoid This 77-year-old male has a generalized eruption with confluent urti- carial plaques and multiple tense blisters. The condition is severely pruritic. or combined with- azathioprine, 150 mg daily, > - COURSE AND PROGNOSIS for remission induction and 50–100 mg for - maintenance; - in refractory cases IVIG: plas- - - Patients often go into a permanent remission mapheresis in milder cases, sulfones (dapsone), after therapy and do not require further therapy; - - 100–150 mg/d. Low-dose MTX 2.5 to 10 mg - local recurrences can sometimes be controlled weekly PO is effective and safe in elderly. In very with topical glucocorticoids; clobetasol with - mild cases and for local recurrences, topical glu- occlusion to urticarial areas. Also, intralesional - cocorticoid or topical tacrolimus therapy may triamcinolone for localized disease. Some be beneficial. Tetracycline ± nicotinamide has - cases go into spontaneous remission without been reported to be effective in some cases. therapy. - 116 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES FIGURE 6-15 (Continued) B. Urticarial plaques and small vescicles and blisters in another patient who had similar eruptions in previous pregnancies. She responded rapidly to systemic glucocorticolds. The delivery was uneventful, and the baby was healthy. DERMATITIS HERPETIFORMIS (DH) ICD-9 : 694.0 ° ICD-10 : L13.0 ! " ! A chronic, recurrent, intensely pruritic eruption occurring symmetrically on the extremities and & - of neutrophils. -- ! Characterized histologically by papillary collection the trunk. ! Granular IgA deposits in paralesional or normal - - ! Consists of tiny vesicles, papules, and urticarial - skin are diagnostic. plaques that are arranged in groups. - ! Responds to sulfa drugs and, to a lesser extent, to - ! Associated with gluten-sensitive enteropathy a gluten-free diet. (GSE). EPIDEMIOLOGY in this disease. Epidermal TG autoantibody probably binds to TG in the gut and circulates Prevalence in Caucasians varies from 10 to 39 either alone or as immune complexes and - per 100,000 persons. deposits in skin. With additional factors IgA - Age of Onset 20 to 60 years, but most com- - activates complement via the alternative path- mon at 30 to 40 years; may occur in children. way, with subsequent chemotaxis of neutrophils - Sex Male:female ratio is 2:1. releasing their enzymes and producing tissue injury. ETIOLOGY AND PATHOGENESIS CLINICAL MANIFESTATION The GSE probably relates to IgA deposits in the skin. Patients have antibodies to transglutami- Pruritus, intense, episodic; burning or sting- > - - - nases (TGs) that - - may be the major autoantigens ing of the skin; rarely, pruritus may be absent.  SECTION 6 BULLOUS DISEASES 117 Symptoms often precede the appearance of skin of neutrophils and eosinophils. Subepidermal lesions by 8 to 12 h. Ingestion of iodides and - vesicle. - overload of gluten are exacerbating factors. Immunofluorescence Of perilesional skin, best Systems Review Laboratory evidence of small- on the buttocks. Granular IgA deposits in tips bowel malabsorption is detected in 10–20%. - - of papillae that correlate well with small-bowel GSE occurs in nearly all patients and is demon- disease. Granular IgA is found in almost-normal strated by small-bowel biopsy. There are usually skin in most patients and is diagnostic. Also no systemic symptoms. found are- C3 and C5and alternative comple- ment pathway components. Skin Lesions Lesions consist of erythematous Circulating Autoantibodies Antireticulin anti- papules or wheal-like plaques; tiny firm-topped bodies of the IgA and IgG types, thyroid antimi- - = vesicles, sometimes hemorrhagic (Fig. 6-16); crosomal antibodies, and antinuclear antibodies - occasionally bullae. Lesions are arranged in - can be present. Putative immune complexes in - groups (hence the name herpertiformis); the 20–40% of patients. IgA antibodies binding to distribution is strikingly symmetric. Scratching the intermyofibril substance of smooth muscles results in excoriations, crusts (Fig. 6-17). (antiendomysial antibodies) are present in most Postinflammatory hyper-and hypopigmentation patients and have specificity for TGs. at sites of healed lesions. Other Studies Steatorrhea (20–30%) and ab- Sites of Predilection Typical and almost diag- - normal D-xylose absorption (10–73%). Anemia nostic: extensor areas—elbows, knees. Buttocks, secondary to iron or folate deficiency. Endos- scapular and sacral areas (Image 6-3 and Figs. copy of small bowel: blunting and flattening - 6-16 and 6-17). Here, often in a “butterfly” of the- villi (80–90%) in the small bowel as in fashion. Scalp, face, and hairline. celiac disease. Lesions are focal; verification is by small-bowel biopsy. LABORATORY EXAMINATIONS DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS Immunogenetics Association with HLA-B8, HLA-DR, and HLA-DQ. - - Grouped papulovesicles at predilection sites Dermatopathology Biopsy is best from early - accompanied by severe pruritus are highly sug- erythematous papule. Microabscesses (poly- gestive. Biopsy of early lesions usually diagnostic, morphonuclear cells and eosinophils) at the but IgA deposits in perilesional skin detected by - - - tips of the dermal papillae. Dermal infiltration IF are the best confirming evidence. Differential FIGURE 6-16 Dermatitis herpetiformis These are the classic early lesions. Papules, urticarial plaques, small grouped - vesicles, and crusts on the elbow of a 23-year-old male. - 118 PART I DISORDERS PRESENTING IN THE SKIN AND MUCOUS MEMBRANES FIGURE 6-17 Dermatitis herpetiformis In this 56-year-old male patient with a generalized highly pruritic eruption, the diagnosis can be made upon first sight by the distribution of the lesions. Most heav- ily involved are the elbows; the scapular, sacral, and gluteal areas; and (not seen in this picture) the knees. Upon close inspection there are grouped papules, small vesicles, crusts, and erosions on an erythematous base and there is postinflam- matory hypo- and hyperpigmentation. Because of pruritus the patient had previ- ously been diagnosed as having atopic dermatitis, scabies, and allergic contact dermatitis and had responded only poorly to topical glucocorticoids. This particular eruption occurred after he had spent a vacation on the Dalmation coast (hav- ing been told that sunbathing would be good for his condition) where his meals consisted of seafood (iodides) and white bread (gluten). diagnosis is to allergic contact dermatitis, atopic - Sulfapyridine 1–1.5 g/d, with plenty of fluids, dermatitis, scabies, neurotic excoriations, papu- if dapsone contraindicated or not tolerated. lar urticaria, bullous pemphigoid, pemphigoid Monitor for casts in urine and kidney function. gestationis (see Table 6-3). & Diet A gluten-free diet may suppress the disease or allow reduction of the dosage of dap- sone or sulfapyridine, but response is very slow. COURSE Prolonged, for many years, with a third of the patients eventually having a spontaneous remission. MANAGEMENT Systemic - Therapy Dapsone 100–150 mg daily, with gradual - reduction to 50–25 mg and often as low as 50 mg- > twice a week. There is a dramatic response, often within hours. Obtain a glucose- - 6-phosphate dehydrogenase level - - before starting sulfones; obtain - methemoglobin levels in the initial 2 weeks, and follow blood counts carefully for the first few months. IMAGE 6-3 Dermatitis herpetiformis. Pattern of distribution.