Unusual clinicopathological and immunological presentation of chronic bullous dermatosis of childhood (linear IgA dermatosis).

Linear IgA bullous dermatosis is a rare sulfone-responsive subepidermal blistering disorder of unknown etiology in which smooth linear deposits of IgA are found in the basement membrane zone. Chronic bullous dermatosis of childhood is equivalent to linear IgA disease of adulthood and is characterized by an abrupt onset of large, widespread and tense bullae on a normal or erythematous base. In this case, we describe an unusual presentation of chronic bullous dermatosis in a 14-month-old Saudi girl. Histopathological examination revealed subepidermal cell poor blisters with linear deposition of IgA, IgG, IgM, and C3 along the dermoepidermal junction. The unusual clinical, histopathological and immunofluorescence findings in this patient are discussed, with an account on the differential diagnosis in such cases along with a detailed review of the relevant literature.

Introduction

Chronic bullous dermatosis of childhood presents in prepubertal, often preschool, children and rarely in infancy. Vesicles or bullae develop on an erythematous or normal base, occasionally giving rise to a so-called string of pearls, a characteristic lesion in which peripheral vesicles develop on a polycyclic plaque.[1] They involve the buttocks, lower abdomen and genitalia and characteristically have a perioral distribution on the face. Oral lesions may also occur.[2] The disorder usually remits by the age of 6-8 years, but in one series, only 12% of the patients experienced persistent disease.[3]

In this case report, we present an unusual example of chronic bullous dermatosis of childhood, characterized by the presence of a subepidermal “cell poor” blister, “fullhouse” deposition of immunoglobulins including prominent deposition of IgA at the dermo-epidermal junction in the absence of other autoimmune and connective tissue disorders.

Case Report

A 14-month-old girl from Saudi was admitted to the dermatology ward because of a 2-month history of skin blistering with severe itching. On examination, multiple vesiculated and crusted skin lesions were found on the extremities, face, mouth, and genitalia [Figure 1]. No skin lesions on trunk or oral mucosa were noted. Also, there was no history of drug intake, fever, or other systemic symptoms. Laboratory test results including serology for autoimmune diseases were negative. A clinical differential diagnosis of chronic bullous disease of childhood and epidermolysis bullosa was made, and biopsies were taken from lesional and prelesional skin for routine histopathological and immunofluorescence studies, respectively.

Figure 1

(a) Chronic bullous disease of childhood. Note the presence of vesicular and crusted skin lesions on the face. (b) Chronic bullous disease of childhood. Eroded and vesicular skin lesions on the external genitalia

Histopathological and immunofluorescence study findings

Histopathological examination of a punch biopsy taken from lesional skin showed a cell-poor subepidermal blister containing scanty lymphocytes and some fibrin strands. The papillary dermis showed evidence of “festooning” with scanty perivascular mononuclear inflammatory cells infiltration. There was no evidence of an increase in polymorphous leukocytes or eosinophils [Figure 2a]. Direct immunofluorescence studies were performed and showed strong linear deposition of IgA, IgG, and C3 at the dermoepidermal junction with similar but moderately strong deposition of IgM (2+) in the same region [Figure 2b]. The C3 deposits extended in a linear fashion to the skin appendages. According to the patient age, clinical distribution of the lesions along with the histological and immunofluorescence findings, a differential diagnosis was made of chronic bullous dermatosis of childhood with an unusual immunofluorescence pattern and a childhood onset of epidermolysis bullosa acquisita (EBA).[4]

Figure 2

(a) Chronic bullous dermatosis of childhood (linear IgA dermatosis). A “cell poor” subepidermal bullae is seen. (H/E stain ×200). (b) Chronic bullous dermatosis of childhood (linear IgA dermatosis). Direct immunofluorescence study showing strong linear deposits of IgA at the dermo-epidermal/basement membrane zone. (Direct IF ×200)

Based on this differential diagnosis, we performed a “salt split test,” which showed deposition of IgG and C3 at the roof of blister. The IgA deposits were slightly split between the roof and base of the bullae. These findings led to a final diagnosis of chronic bullous dermatosis of childhood (linear IgA bullous dermatosis), with an unusual immunofluorescence pattern that is rarely described in the literature.[356]

Discussion

Chronic bullous dermatosis of childhood is the most common chronic bullous dermatosis in the first 10 years of life. The disease commonly involve the perioral skin, lower trunk, inner thighs, genitalia and perineum.[1-3] The mucous membranes may also be affected. Bullae are the major clinical finding, and their appearance is characteristic with an annular arrangement of sausage-shaped bullae around resolving crusted lesions.[7] Pruritus can be mild to severe. The disorder is self-limiting and clears up within several months to three years. It is not usually associated with celiac disease. However, associations with ulcerative colitis,[8] certain medications[39] . sarcoidosis,[10] lymphoproliferative,[11] and immune-mediated diseases[12] have been described.

The clinical and histopathological differential diagnosis usually includes dermatitis herpetiformis, childhood form of EBA and bullous pemphigoid. In our case, the major concern was the missing of a diagnosis of childhood onset EBA. However, the presence of strong linear deposition of IgA at the dermoepidermal junction and the results of the salt split test helped eliminate this possibility. Furthermore, the presence of associated deposits of IgG, IgM, and C3, which was confirmed by immunofluorescence studies in the absence of an associated autoimmune systemic disease is a rare event in this disorder and has only partially been reported previously in the literature. The cases described by Petersen et al.[5] and Powell et al.[13] had only deposits of IgA with associated IgG appearing in the early stages of the illness while our case has confirmed “fullhouse” deposition of Ig's and C3. The lack of eosinophilic infiltration, besides the presence of IgA deposits excludes an early onset of bullous pemphigoid. We also believe that the cell poor appearance of the blisters in this condition could be due to the “age of the illness,” as suggested by the 2-month history of the eruption.

Summary

Chronic bullous dermatosis of childhood is a common blistering disease, which can be seen in infants and preschool children. Both dermatopathologists and clinical dermatologists should be aware of the unusual and rare histopathological and immunofluorescence features, which can be seen in such cases and may lead to an erroneous diagnosis of a more severe disorder like childhood EBA.