Chapter 10 10 Differential Diagnosis of Atopic Eczema

B. Wedi, A. Kapp

10.1 Table 10.1. Differential diagnosis of atopic eczema Introduction Chronic inflammatory skin diseases Contact (allergic, irritant) Several studies demonstrate our difficulties in estab- Seborrhoeic lishingthediagnosisofatopiceczema(AE).Itsun- Lichen simplex chronicus known aetiology, the wide range in symptomatology, and the fluctuating course, including the many eliciting Infectious agents Candida factors, form the background for these difficulties [1]. During the past few decades, several proposals have been made to establish diagnostic criteria for AE Staphylococcus aureus [2–5]. The main problem of most criteria is that they Sarcoptes scabiei HIV-associated dermatitis are not applicable to both adults and children and do Immunologic disorders not discriminate between the allergic IgE-mediated and the nonallergic type of AE [6, 7]. foliaceus The differential diagnosis of AE is closely related to Graft-versus-host disease theageofthepatient.Itincludesotherformsofecze- Dermatomyositis ma, immunodeficiencies associated with eczematoid Malignant Diseases ,infectiousdiseasesand infestations, metabolic Cutaneous T-cell lymphoma (, S´ezary syndrome) diseases, neoplastic diseases and other chronic inflam- Histiocytosis X (Letterer-Siwe disease) matory skin conditions (Table 10.1). Congenital disorders Netherton’s syndrome Dubowitz syndrome 10.2 Erythrokeratodermia variabilis Chronic Inflammatory Skin Diseases Immunodeficiencies Wiskott-Aldrich syndrome (immunodeficiency with thrombocytopenia and eczema) “Eczema” is a nonspecific term often confounding the Thymic hypoplasia (DiGeorge syndrome) clinical and histopathologic description of various Hyper-IgE syndrome unrelated inflammatory diseases. All eczemas are his- Severe combined immunodeficiency (SCID) tologically spongiotic, but not all spongiotic dermato- Ataxia teleangiectasia ses are clinically eczematous. The histology is mainly Metabolic Diseases noncontributive to the diagnosis, as there are no defi- Phenylketonuria Tyrosinemia nite features allowing us to distinguish between AE and Histidinemia other forms of eczema. The eczematous eruptions all manifest T-cell proinflammatory mediator involve- Pyridoxine (vitamin B6) and niacin deficiency ment, yet may be quite different clinically [8]. Multiple carboxylase deficiency Differentiating from AE may Nonallergic reaction to medication be difficult in an infant less than 6 months old. The dif- Infliximab 10.4 Immunologic Disorders 101 ferential diagnosis of AE and seborrheic dermatitis is such as sinusitis, asthma, and hyper-IgE syndrome, most often complicated by the seemingly definite seb- and laboratory abnormalities such as elevated IgE lev- orrheic dermatitis developing into the later condition. els, eosinophilia, and possible TH1-TH2 imbalances, Seborrheic dermatitis is characterized by onset during suggestapredilectionforatopicdisordersinthese the 1st days or weeks of life, absence of pruritus, and patients. presence of greasy scaling on a yellow-red base. Involvement of the top of the scalp (), axilla, and diaper area makes it more likely the patient has 10.4 seborrheic dermatitis, whereas excoriated dermatitis Immunologic Disorders involving the extensor surfaces, face, and trunk favour AE. Dermatitis herpetiformis Duhring (DHD) is an IgA- In patients with well-established AE who become mediated blistering skin disease characterized by the resistant to therapy, the possibility of contact dermati- presence of granular deposits of IgA in papillary der- tis to the topical therapy, including allergy to cortico- mis. The skin may resemble AE lesions and is glu- steroid or a preservative, should be considered [9, 10]. ten-dependent. Less than 10% of patients with DHD Inthesepatientspatchtestingshouldexcludeallergic have gastrointestinal symptoms suggestive of coeliac , particularly in the case of localized disease, yet they all have gluten-sensitive enteropathy lesions.Interestingly,inanAustraliancontactdermati- [16]. tis clinic, approximately 20% of total cases consisted of Pemphigus foliaceus is an acquired superficial blis- AE without patch test positivity [11]. Three distribu- tering skin disease in which IgG autoantibodies target tion patterns predominated in this study: generalized the extracellular region of desmoglein 1, a member of dermatitis and dermatitis involving only the hands or the desmosomal cadherin family, responsible for adhe- face. sive function [17]. Due to superficial blistering, intact bullae are rarely found. Therefore, the skin lesions that are often distributed in seborrheic areas can mimic 10.3 acute/subacute eczema. Infection and Infestation The skin symptoms of graft-versus-host disease (GvHD) may resemble AE. may be misdiagnosed at any age with AE in Acute GvHD occurs during the first 100 days after presence of highly pruritic, erythematous papular transplantationinupto50%ofgraftrecipients,while lesions. In most cases, the typical burrows can be found chronic GvHD develops in about 30%–50%, usually on the flexor wrists, finger webs and genitalia. Similar within 100–500 days following allogeneic stem cell symptoms in other family members may point to the transplantation [18]. It can involve the skin, liver, gas- diagnosis scabies. Otherwise there is an enhanced sus- trointestinal tract, and less frequently the lungs, eyes ceptibilitytoinfectionwithSarcoptes scabiei in atopic and neuromuscular system. Initial symptoms of acute patients. GvHD may be pruritus and dysaesthesia or pain of the In addition, dermatophytosis and as palms, soles and ears. Maculopapular exanthemas of well as infection with Herpes simplex and Staphylococ- the face, palms and soles are frequently seen. Acral and cus aureus maybeconfusedwithskinlesionsofAE. perifollicular and involvement are typical. In Complicating the differential diagnosis, patients suf- addition, xerostomia and manifestations can be fering from AE are predisposed to these infections and seen. infestations [10, 12, 13]. Initial symptoms of chronic GvHD may be a persis- Diseases of the skin are important signs of HIV tenterythemaofthefacewithpigmentation.Chronic infection in which dermatitis and eczema present GvHD may be limited or extensive, localized (about mostly as seborrheic dermatitis. In children with pae- 20%) or generalized (about 80%). Progressive chronic diatric AIDS, AE has been described in up to 50% of GvHD immediately follows acute GvHD (about 32%); cases[14].HIV-infectedadultscommonlydevelopa delayed chronic GvHD occurs after a disease-free inter- condition that strongly resembles AE and is some- val (about 36%) and de novo chronic GvHD occurs times called atopic-like dermatitis [15]. Conditions without prior acute GvHD [18]. 102 10 Differential Diagnosis of Atopic Eczema

Localized chronic GvHD resembles lichen ruber ders including eczema. It can present clinically as planus, in about 3% a or et patches, plaques, tumors or generalized erythroderma atrophicus. The generalized form is characterized by [21, 22]. Even though the prognosis is good in most scaly , telangiectasias and pigment anoma- patients with patch-stage disease, extracutaneous lies. Chronic disseminated GvHD may be lichenoid or spread involving any organ is possible and may eventu- sclerodermiform. Most cases show Wickham’s striae of ally lead to death. S´ezary syndrome is a systemic vari- the buccal mucosa. In about 40% of cases, the nails are ant and manifests as erythroderma with generalized involved. bright red, scaling skin and associated leukemia and The skin findings in dermatomyositis are character- lymphadenopathy. Multiple biopsies may be necessary istic,butinitiallytheymaybeconfusedwithatopic to confirm the diagnosis. Immunophenotyping and T- eczema. Dermatomyositis is an immune-mediated dis- cell receptor gene arrangement analysis confirming a ease of the muscle and the surrounding connective tis- malignant clone are sometimes helpful in diagnosis. sue which is more common in female patients. It is Moreover, in preexisting nonclassified chronic palmo- associated with an increased risk of cancer. plantar eczema that responds poorly to standard thera- The skin findings in dermatomyositis are character- pies, differential diagnosis of mycosis fungoides-type ized by a lilac discoloration of the eyelids (heliotrope cutaneous T cell lymphoma of the hands and soles rash), often with periorbital edema, and erythematous should be considered [23]. papules over knuckles (Gottron sign), elbows, knees, and upper chest and back. These lesions are frequently Histiocytosis X (Letterer-Siwe Disease). Though prin- photosensitive. Dilated nail-fold capillary loops can be cipally a paediatric disease, Langerhans cell histiocyto- found at the base of the fingernails. Although proximal sis can affect any age group. It can be unifocal (skeletal) and symmetrical muscle weakness is typical, skin or multifocal (skeletal and/or visceral). Head and neck lesions may exist without inflammatory myopathy manifestation may mimic eczema and can thus be mis- (amyopathic dermatomyositis) [19]. Interestingly, in diagnosedasAE.Typicalskinsymptomsarecrusted children the heliotrope rash and Gottron papules clas- purpuric papules and a scaly seborrhoeic-like eruption sically associated with dermatomyositis appeared less in the scalp and groin. The disease can vary from a mild commonly than a rash on the extremities and periun- cutaneous-only eruption to a severe, life-threatening gual [20]. systemic disease. Myositis-specific autoantibodies such as Anti-Jo-1, anti-SRP and anti-Mi-2 may be present as antinuclear antibodies, increased levels of immunoglobulins. Cre- 10.6 atinine kinase and aldolase levels may not be elevated Congenital Disorders on initial presentation. Netherton’s syndrome is defined by a triad consisting of congenital ichthyosiform dermatitis with defective 10.5 cornification, trichorrhexis invaginata (bamboo hair) Malignant Diseases and severe atopic diathesis with high serum IgE levels and hypereosinophilia. It was originally described by Unexplained eczema of adult onset may be associated Dr. E.W. Netherton in 1958 [24]. with an underlying lymphoproliferative malignancy. Life-threatening complications during infancy When a readily identifiable cause (e.g. , contact- include temperature and electrolyte imbalance, recur- ants, drugs) is not found, a systematic evaluation rent infections, and failure to thrive. Genetic linkage of should be pursued. Patients should be evaluated with a theautosomalrecessivedisorderhasbeenestablished careful physical examination, complete blood counts, to the SPINK5 gene locus on chromosome 5q32 encod- peripheral blood smears, chest roentgenography, com- ing the serine protease inhibitor LEKTI (lymphoepi- puted tomography of the chest and abdomen, and thelial Kazal-type-related inhibitor), which is involved serum protein electrophoresis. in T-cell differentiation [25]. Cutaneous T-cell lymphoma (mycosis fungoides, ThetrueincidenceofNetherton’ssyndromemight S´ezary syndrome) mimics several benign skin disor- be as high as 1/50,000, often unrecognized due to chal- 10.7 Immunodeficiencies 103 lenging diagnostic problems during infancy and early tor retardation and lack of eczema to a condition of childhood and overlapping features with AE and other severe intrauterine growth retardation, mental retar- recessive ichthyoses [25]. dation, microcephaly, and uncharacterized eczema- Skin symptoms are present at birth or develop with- tous skin lesions in 40% [29]. in the first postpartum days or weeks and can range from linearis circumflexa Comel (ILC) in milder cases to congenital ichthyosiform erythroderma 10.7 (CIE), which may resemble enteropathi- Immunodeficiencies ca or Leiner’s disease [26]. The skin lesions are often pruritic,resembleatopiceczema,butdonotrespondto Any patient presenting with an eczematoid skin rash topical corticosteroid treatment and show an unstable, dating from the 1st month of life should be carefully undulating course. ILC appears as erythematous migra- followed for the possibility of an immunodeficiency tory patches surrounded by serpiginous double-edged disorder, particularly if recurrent infections and failure scales which are usually found in flexural areas. Patients to thrive complicate the clinical course. Most of these also have skin findings suggestive of AE, such as liche- conditions could be diagnosed by means of screening nification and scaling. The scalp is usually quite scaly, for lymphopenia or for T-cell deficiency in cord blood but nails and teeth are usually not involved. White der- at birth. Long-term prognosis is poor; few patients sur- mographism is not present [26]. vive beyond their teens. Skin lesions are usually accompanied by hair shaft Wiskott-Aldrich syndrome is a condition with vari- abnormalities that develop during early childhood and able expression characterized by a mixed humoural may result in diffuse alopecia. The hallmark is trichorr- andcellularimmunedisorderassociatedwithaflexur- hexis invaginata (bamboo hair), but other abnormali- al rash indistinguishable from AE. The diagnosis is ties, including pili torti (twisted hair) and trichorrhexis usually suggested by haemorrhagic diathesis associat- nodosa (hair of varying diameter), have been observed. ed with small platelets and commonly includes immu- However, there can be several similarities to AE, i.e. noglobulin M deficiency. It represents an X-linked frequent eczematoid appearance, onset in infancy, fre- (Xp11.22) recessive syndrome, thus found almost quent pyogenic superinfection, elevated total serum IgE exclusively in boys, characterized by eczema, thrombo- levels, concomitant food allergies, anaphylactoid reac- cytopenic purpura with normal-appearing megakar- tions, and respiratory allergy, including asthma. T-cell yocytes but small defective platelets, and undue sus- numbers are reduced and the T-cell response is im- ceptibility to infection [30]. Atopic symptoms are fre- paired, whereas peripheral eosinophilia is common [26]. quently present, and eczema develops in 81% of Clearly excluding the differential diagnoses may patients. and recurrent infections also be of importance with respect to treatment. For usuallyalsodevelopduringthe1styearoflife.The example, it has been shown that children with Nether- eczema may improve as the patient gets older, although ton’s syndrome who responded to treatment with 0.1% serious complications such as secondary infection (e.g. tacrolimus ointment had substantial percutaneous , ) or erythroderma can occur. Infec- absorption of the drug, with serum concentrations well tions, , and bleeding are major causes of above the therapeutic range [27]. Therefore, it has been death, but the most common cause currently is EBV- recommended that the diagnosis of Netherton’s syn- induced lymphoreticular malignancy [30]. The genetic dromeshouldbeconsideredinanyinfantorchildwith basisofthediseaseisamutationinthegeneforthe extensive erythroderma resistant to treatment and Wiskott-Aldrich syndrome protein (WASP), which is these patients should be monitored for blood tacroli- found only in blood cells and is involved in the organi- musconcentrations[28]. zation of the actin cytoskeleton [31]. Interestingly, in Dubowitz syndrome is an autosomal recessive dis- Wiskott-Aldrichsyndrome,thereisadefectiveexpres- order defined by a syndrome phenotype on the basis of sion of CD43 in blood mononuclear cells, which clinical descriptions. The facial appearance is charac- appears to be rather increased in atopic eczema [32]. In teristic and present in most patients. The phenotypic classic Wiskott-Aldrich syndrome, IgM levels are low spectrum is quite variable and ranges from normal and IgG levels are relatively normal, but IgA and IgE growth and head circumference with mild psychomo- levels may be elevated. 104 10 Differential Diagnosis of Atopic Eczema

Thymic hypoplasia (DiGeorge anomaly) is a congen- should be considered in children with staphylococcal ital immunodeficiency that is usually diagnosed shortly pneumonias or recurrent complicating after birth because of abnormal facies, hypocalcaemia chronic eczema. The rash is typically pruritic, often or cardiac manifestation. However, it may be confused lichenified, and in a distribution atypical for true AE. with AE because severe eczema can be present [33]. Thedermatitiswilloftenimprovewithprophylactic DiGeorge anomaly is associated with microdeletions antibiotics alone, unlike atopic dermatitis [36]. from chromosome 22q11.2 and leads to hypoplasia or Severe combined immunodeficiency (SCID) is a aplasia of the thymus and parathyroid glands, often fatal syndrome of diverse genetic cause characterized associated with anomalies of the great vessels, oesopha- by profound deficiencies of T- and B-cell (and some- geal atresia, bifid uvula, upper limb malformations, times NK-cell) function [30]. During the first few congenital heart disease, a short philtrum of the upper months of life, infants present with frequent periods of lip, hypertelorism, an antimongoloid slant to the eyes, diarrhoea, pneumonia, otitis, sepsis, and cutaneous mandibular hypoplasia, and low-set, often notched ears infections. X-linked SCID is the most common form, [30]. Phenotypically similar syndromes are collectively although mutated genes have been demonstrated on grouped under the acronym CATCH-22 (cardiac several autosomal chromosomes [30]. defects, abnormal facies, thymic hypoplasia, cleft pal- ate, and hypocalcaemia resulting from 22q11 dele- tions).DiGeorgeanomalyisthemostfrequentcontigu- 10.8 ous gene deletion syndrome in humans occurring in Metabolic Diseases about one case per 3,000 persons. Depending on T-cell proliferative response to mito- Eczematous skin lesions have been described in a vari- gens, DiGeorge anomaly can be classified as partial or ety of hereditary or nutritional metabolic disorders. complete.Patientsareusuallyonlymildlylymphope- However, in rare diseases, e.g. histidinaemia, prolidase nic,butthepercentageofCD3+Tcellsisvariably deficiency, Hartnup’s disease (hereditary aminoacid- decreased. Immunoglobulin concentrations are usual- uria), and multiple carboxylase deficiency, precise data lynormal,althoughIgEmaybeelevated. with respect to AE and/or atopy are lacking. Total serum IgE levels up to several thousand units In up to 50% of cases with phenylketonuria, eczema- per millilitre give a differential diagnosis with the tous lesions indistinguishable from AE lesions occur hyper-IgE syndrome, which is characterized by scalp during the 1st year of life and clear with appropriate diet and face eruptions with fine papular and sometimes avoiding phenylalanine. The disease is caused by muta- pustular skin lesions and chronic eczematoid dermatitis tionsinthephenylalaninehydroxylase(PAH)gene, usually manifesting itself early in life, and is often com- resulting in elevated concentrations of phenylalanine plicated by deep tissue infections such as skin and respi- and phenylalanine metabolites (phenylketones) in the ratory staphylococcal abscesses, sometimes associated body fluids. This autosomal recessive disorder demon- with candidiasis [34,35]. The bacterial infections gener- strates extensive genetic and clinical variability, occurs ally commence in infancy or early childhood involving in one of 15,000 births and is most common among per- the skin and sinopulmonary tract. The “cold” abscesses sons of Western European background [37]. Untreated, (large fluctuant mass, that is neither hot nor tender and affected individuals develop severe to profound mental is not associated with fever or signs of inflammation) disabilities, behavioural difficulties, seizures, rashes, are occasionally seen and are pathognomic but not pigment dilution, and an unusual body odor. essential to the diagnosis. There is typically an absence Acrodermatitis enteropathica is a rare autosomal of atopic symptoms, wheeze or family history of atopy. recessive disorder caused by impaired absorption of Coarse facies, mild eosinophilia, lymphomas, cryp- zinc from the gastrointestinal tract. It is characterized tococcal meningitis, neutrophil chemotactic dysfunc- by acral and periorificial dermatitis, alopecia and diar- tion, and mucocutaneous or systemic fungal disease rhoea, although the complete presentation is seen in are variable features [35]. only 20% of patients [38]. Retardation of growth and Theimportanceofclinicaldifferentiationofhyper- secondary infections are frequently observed. Mor- IgE syndrome from AE is important because treatment phologically, erythematous scaly plaques and eczema- and prognosis are different. Hyper-IgE syndrome tous or vesiculobullous lesions can be found. Nail 10.8 Metabolic Diseases 105 t Middle None Atypical, flexor wrists, finger webs, genitalia Rare Rare Similar sym- ptoms in family members Rare Normal to high Rare None Uncommon Phenylketonuria Scabies 1/15,000 births; most common in Western Europe Chromosome 12q24.1, PAH gene mutati- ons, extensive ge- netic variability Phenylalanine and metabolites are elevated in body fluids Indistinguishable from AE lesions, clears with diet avoiding phenyla- lanine ties, seizures, pigment dilution, unusual body odor Normal Mental disabili- t DiGeorge syndrome At birth First year of life Any age Male = female male = female Male = female 1/3,000, most frequent gene deletion syndro- me in humans Chromosome 22q11 deletions Defective T-cell function, hypo- calcaemia in 60% Atypical, may be severe Common, serious Uncommon disease, thymus hypoplasia, hy- po-parathyroi- dism Uncommon Uncommon Frequen Common None Uncommon live Wiskott-Aldrich syndrome years, rare cases are first detected in adults vely males male births Chromosome Xp11.22–23, WASp gene mu- tations IgM deficiency, small platelets, reduced CD43 on lymphocytes In 81% of pa- tients, responsi- ve to topical ste- roids serious Common Common Common Uncommon About 50% Hyper-IgE syndrome 1–8 weeks At birth or first Male = female Almost exclusi- deletions Extremely high May be elevated May be elevated Absent Neutrophil che- motactic defect Atypical, scalp and face erupti- ons, chronic ecze- ma typically pru- ritic, often licheni- fied Deep-seated (sepsis) “Cold“ abscesses Bleeding Congenital hear Absent Common, serious Common, infancy Dubowitz syndrome At birth or first years male Unknown Chromosome 4q elevated Uncharacte- rized Male = fe- Rare Very rare 4/1million Mental retardation, growth re- tardation Common Common None Uncommon Uncommon Hair shaft ano- Chromosome Netherton’s syndrome At birth or first days to weeks 1/50,000 births 5q32, SPINK5 gene mutation of LEKTI Resistant to topical cortico- steroids Superficial (skin) Frequent Possible Frequent malies Rare Common matitis weeks Normal Very high May be Axillae, diaper area, often not pruritic and not excoriated Rare None Male = female Male = female Male = female Unknown None high phology and distribution (age-depen- dent), pruritic, excoriated Superficial (skin) Common Uncommon Absent Common Uncommon Common Synopsis of some differential diagnoses of atopic eczema in early FeatureAgeofonset >2months Atopic eczema Firstdaysor Seborrheic der- Sex Prevalence Common Common Genetic abnormality IgE level Normal to very Eosinophilia Frequent Uncommon Other laboratory findings Eczema Typical mor- S. aureus infection Other infection Rare White dermo- graphism Respiratory all- ergy Food allergy Common Uncommon Coarse facies None Other findings Table10.2. 106 10 Differential Diagnosis of Atopic Eczema

changes such as onychodystrophy, onycholysis, and there is still no objective laboratory or genetic test for , and oral and ocular manifestations such as establishing the diagnosis of AE, which continues to be stomatitis, perl`eche, blepharitis, conjunctivitis, and based on the presence or absence of a constellation of photophobia may occur. signs and symptoms. Several other proposals to opti- Very recently, nonallergic reactions to medication mize clinical criteria have been made but have failed to resulting in AE-like eruption have been published. Two be applicable in every clinical setting. Clinical criteria cases were reported in which successful treatment with are imprecise and no amount of mathematical, statisti- infliximab for rheumatoid arthritis precipitated AE- cal manipulation or validation will make them precise. likeskinlesions[39].Inbothcasestheskinreaction This may explain our difficulties in the differential was nonallergic. Infliximab’s mechanism of action diagnosis of AE. involves alteration of the cytokine pattern with sup- We have clearly gained new insights into the immu- pression of type 1 T-cell response and thus infliximab nologic pathophysiology of AE, i.e. the role of T lym- therapy may result in a type 2 T-cell pattern which is phocytes, particularly CD4+ and CD8+, eosinophils characteristic for AE. and antigen-presenting cells, and we now know that A synopsis of the most important differential diag- the role of specific sensitization is more and more nosesininfancyandadulthoodisgiveninTable10.2 questionable in the manifestation and course of AE. and Table 10.3, respectively. Thus, perhaps future diagnostic strategies may be based upon immunologic changes found in both the nonallergic as well as the allergic type of AE, but not in 10.9 other eczematous conditions such as immunodeficien- Conclusion cies associated with eczematoid rashes, infectious dis- eases and infestations, metabolic diseases, neoplastic More than 20 years have passed since the publication of diseases and other chronic inflammatory skin condi- Hanifin and Rajka’s criteria for the diagnosis of AE, but tions.

Table 10.3. Synopsis of some differential diagnoses of atopic eczema in adults Feature Atopic eczema Seborrhoeic T-cell Contact Scabies Pemphigus GvHD dermatitis lymphoma dermatitis foliaceus Age of onset Any age Any age 50–60 years Any age, Any age Middle age Any age mostly adults IgE level Normal to Usually Usually high Usually May be Usually Usually very high normal normal elevated normal normal Eosinophilia Common Rare Rare Rare Common Rare Uncommon Eczema Typical mor- Atypical, Atypical, per- Often Involvement Atypical, in Atypical, phology and seborrheic sistent scaly localized of flexor wrists, seborrheic papulosqua- distribution, areas, often patches poorly finger webs areas, super- mous erup- pruritic, often not excoriat- responding to and genitalia, ficial tions, liche- excoriated ed and not topical steroids typical burrows noid pruritic White der- Common Rare Rare Rare Rare Rare Rare mographism Pruritus Typical Rare Common Possible Typical Uncommon Common Respiratory Common Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon allergy Food allergy Common Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Other T-cell receptor Positive Similar symp- IgG auto- findings rearrangement patch test toms in family antibodies to members desmoglein 1 References 107

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