Rituximab efficacious in chronic bullous disease of childhood: IDOJ

Linear IgA disease (LAD) also known as chronic bullous disease of childhood (CBDC) is the most common autoimmune blistering disease in infants and children. Usually, children of CBDC respond very well to oral dapsone along with topical steroids. In refractory cases, reports of many systemic drugs like erythromycin, tetracycline, nicotinamide etc have been employed successfully. Rituximab, a chimeric monoclonal anti‑CD20 antibody acting by cell‑mediated and complement‑dependent cytotoxicity which has proved efficacy in many immunobullous disorders. Recently a case report of a child with CBDC being successfully treated by rituximab was published in the Indian Dermatology Online Journal.

A 2‑year‑old male child, presented with history of recurrent blisters from the last 18 months. Dermatological examination revealed multiple, tense, discrete as well confluent vesicles, bullae and few erosions all over the body, particularly more intensively distributed over the buttocks, perineal region and lower limbs. New crops of lesions used to appear along the periphery of healed or crusted lesions. The characteristic annular arrangement of the vesicles/bullae around a crusted, erythematous plaque, described as 'string of pearls sign' or 'cluster of jewels', was seen in many sites, There was associated history of recurrent oral ulcers and redness of eyes of same duration. The palms, soles and genital mucosae were spared.

Initially, blisters used to heal over 2 to 3 weeks spontaneously but from the last 9 months he was not disease free. The child had a past history of developing drug hypersensitivity to dapsone 5 months back so dapsone was discontinued. He was administered systemic corticosteroid, erythromycin, cyclosporine, methotrexate, and IVIG over the last 6 months without much benefit.

All routine investigations were essentially normal. Histopathology revealed subepidermal bulla with predominantly neutrophilic infiltration within the bulla and underlying upper dermis composed of neutrophils, eosinophils, and some lymphocytes. Direct immunofluorescence of the perilesional skin revealed linear deposition of IgA (++) along the basement membrane zone. Based on the clinical, histopathological, and immunopathological features, a diagnosis of chronic bullous disease of childhood was made.

Considering the recalcitrant disease the patient was planned for rituximab. Injection rituximab infusion 200 mg was administered over 5–6 hour duration. Two doses of rituximab were given at 15 days intervals. The dose was calculated based on rituximab protocol for Paediatric Rheumatology issued by Oxford Paediatric and adolescent Rheumatology Centre at 375mg/m2 and estimated body surface area of 0.53m² for 11 kg weight. The skin lesions dried up without any scarring or residual deformity in the next 15 days. The patient was followed up every month for the next 12 months. The patient was disease free till three and half year of age.

CBDC is considered to be the childhood variant of adult‑onset disease Linear IgA disease because of overlapping immunogenetics and immunopathology. The most probable pathological mechanism for CBDC is IgA‑and complement‑mediated neutrophil chemotaxis creating a split at DEJ. The drugs like vancomycin and cephalosporine have been implicated in few case reports.

Usually CBDC responds very well to first‑line treatment like oral dapsone and topical steroid. Most children go into complete remission within 2 years of disease onset and only very rarely the disease persists after puberty even after multiple modalities of therapies. Dapsone rarely can cause serious drug reaction leading to drug rash, eosinophilia, systemic symptoms (DRESS) also known as dapsone hypersensitivity syndrome or drug hypersensitivity syndrome. Recent studies also report successful management of recalcitrant adult‑onset linear IgA disease with rituximab. Similarly rituximab proved to be safe and effective in this paediatric patient.

In conclusion rituximab can be an effective and safe option in a case refractory CBDC failing traditional treatments,, provided guidelines are followed to prevent any side effects.

References-

1. Mitra D, Bhatnagar A, Singh GK, Sandhu S. Successful treatment of refractory chronic bullous disease of childhood with rituximab. Indian Dermatol Online J 2022;13:248-51.