Dermatitis herpetiformis as the only manifestation of celiac disease: case report and literature review

Aims: To present a case of dermatitis herpetiformis, a papulovesicular rash due to deposits of immunoglobulin A in the papillary dermis. This is a common extraintestinal manifestation of celiac disease, although rare in childhood. Case description: A 10-year-old girl was diagnosed with celiac disease, suspected only due to the occurrence of typical lesions of dermatitis herpetiformis. Intestinal biopsy demonstrated total atrophy of duodenal villi in spite of the lack of clinical digestive manifestations. Under a gluten-free diet the patient presented favorable evolution, with regression of cutaneous lesions. Conclusions: Dermatitis herpetiformis is a common manifestation of celiac disease, but is not frequent in infants. Therefore, is very important to investigate any child that presents a chronic papulovesicular cutaneous eruption non-responsive to usual treatments in order to perform a precocious diagnosis of celiac disease, avoiding its serious repercussions.


INTRODUCTION
Celiac disease (CD) is an autoimmune enteropathy triggered in genetically susceptible individuals by gluten ingestion.6][7][8][9] The CD affects usually Caucasian individuals and women in a 2:1 proportion. 6n its classical presentation the beginning of CD symptoms occurs generally in 6 to 24 months old children and is characterized by chronic diarrhea, abdominal pain, abdominal distension, insufficient growth, anorexia and vomiting. 4,6,10However, many individuals can be asymptomatic and are diagnosed only after years of silent disease. 2,10Atypical manifestation of CD include extraintestinal changes as iron-deficient anemia, osteoporosis, and cutaneous and neurological manifestations. 2,4,6,11,12][15] An occurrence of the association between alterations in the jejune mucosa and the deposit of immunoglobulin A (IgA) in the papillary dermis was described in 1966. 16,17This pathology was the dermatitis herpetiformis (DH), which is characterized by urticarial bullous lesions (often excoriated by pruritus) associated to gluten-sensitive enteropathy, being symptomatic or asymptomatic. 4,18he present study describes the case of a patient with CD diagnosis, suspected due to typical lesions of DH, with favorable evolution with a gluten-free diet, showing regression of cutaneous lesions.

CASE REPORT
A 10 years-old, female patient presented pruritic lesions on the skin with six months of evolution and without response to treatment with corticosteroids and antifungals.Biopsy was performed by a dermatologist with the result compatible with DH, being referred to the pediatric gastroenterologist to rule out a diagnosis of CD.There were no clinical signs and associated symptoms such as weight loss, pain, restricted growth and gastrointestinal manifestations.Family history was negative for CD and previous medical history had no particularities.On physical examination, the patient was in good general condition, afebrile, with height and weight appropriate for age.She presented erythematous lesions on the extensor region of elbows and knees bilaterally (Figure 1).No other changes were observed in the physical analysis.Antitransglutaminase IgA value was 80U (referential value 18U).Blood count, hepatic, renal and pancreatic functions had no changes.The patient underwent endoscopy with biopsies taken.Histopathological examination revealed mild chronic esophagitis with intraepithelial eosinophils, mild antral chronic gastritis with negative Helicobacter pylori research.Duodenal biopsy revealed increased intraepithelial lymphocyte population, crypts hyperplasia and villi shortening (Figure 2).The histopathological and clinical aspects of duodenal biopsy were identified as a category 3B of Marsh-Oberhuber classification for CD.A gluten-free diet was introduced with the confirmed diagnosis.The patient presented favorable clinical evolution with total regression of lesions.

DISCUSSION
9][20][21] Certainly variations exist, and bullous, pustular or eczematous lesions can be found sometimes. 22Lesions are symmetrically distributed and commonly found on elbows, knees and buttocks, but may also occur in the upper back, leather scalp, abdomen, groin and face. 4,9The average age of diagnosis of DH is 30 to 40 years, with unusual appearance of lesions before puberty.][25] The association of DH with CD was initially described by Marks et al. 16 in 1966, and nowadays the rash of DH appears to represent an external marker of intestinal sensitivity, defined as an extraintestinal manifestation of CD. 4,9,10 Approximately 10% of individuals who have CD manifest lesions of DH, and among individuals with DH, the prevalence of changes compatible with CD by biopsy of the small intestine is 60% to 80%, 9 reaching 93% if the increase of intraepithelial lymphocyte count in intestinal microvilli is considered a diagnostic criteria. 19However, only 10-20% have classic symptoms of malabsorption. 4,18,21he pathogenesis of DH is still unclear, but as in CD, there is an immune response induced by gluten sensitivity. 22,23,26DH and CD are closely related diseases, in which the main autoantigens are distinct, but share common epitopes. 26The tissue transglutaminase (tTG) was identified as the autoantigen prevalent in CD, 27 while in the DH, the predominant autoantigen is the epidermal transglutaminase (eTG). 26,28,29Sardy et al. 26 proposed that the DH pathogenesis consists of immune response of low avidity for tTG, resulting initially in silent CD, that with continued exposure to gliadin, leads to the development of populations of antibodies with high affinity to eTG for cross-reactivity, which manifests as DH.][32][33] DH is diagnosed through biopsy of the lesions showing a subepidermal blister with a predominantly neutrophilic infiltrate in the dermal papillary tips, although a mixed or even predominantly lymphocytic dermal infiltrate may also be found. 22Direct immunofluorescence reveals granular deposition of IgA at the dermo-epidermal junction in both involved and uninvolved skin as well as the oral mucosa. 4,18,19,26erologic testing is a useful adjunct for diagnosis and may be used to monitor the therapy response. 29,34ntigluten, antiendomysium, antigliadin and tTG antibodies have been detected in patients with DH, however, tTG and eTG are considered the target autoantigens in DH. 35 Heil et al. 34 demonstrated that anti-tTG IgA can be useful for screening, because it is very disease-specific (100%) and sensitive (95% CD/96.6%DH) for the diagnosis of gluten sensitivity, while anti-eTG IgA was also very specific (100%), but was present in only 15% of CD cases and 44.8% of DH cases.After the diagnosis of DH, it is necessary to determine who has associated CD.The gold standard for CD diagnosis is biopsy of the intestine, which is recommended for all individuals with DH. 9,10,23 Treatment for DH, as well as for CD, consists in removing gluten from the diet. 6,8,9,11Associated with this therapy, suppressive treatments can be used, such as dapsone at a dose of 25-100 mg per day for a short period of time to control local symptoms and reduce the number and severity of skin injuries. 4,9,18,20,23,36n this patient, diagnosis was suspected due to the typical pattern of injury, being established the glutenfree diet with favorable evolution of skin lesions.DH should be considered in any child who presents chronic papulovesicular rash of unknown origin which is not responsive to simple measures.Its recognition leads to early diagnosis of CD, which is very important considering the great impact that this disease may present.

Figure 2 .
Figure 2. Results of duodenal biopsy showing short villi and long crypts characteristic of celiac disease.

Figure 1 .
Figure 1.Erythematous and papular lesions with hematic crusts and hypopigmented scars on knees, characteristic of dermatitis herpetiformis.

Table 1 .
Systematic review of the literature performed on September, 2013 Sgnaolin V et al. -Dermatitis herpetiformis as the only manifestation of CD MeSH = Medical Subject Headings; DeCS = Descritores em Ciências da Saúde.