Pemphigus foliaceus (PF) is an acquired autoimmune blistering disease with autoantibodies targeted against desmoglein-1. PF typically presents in adults who are 40–60 years of age. Other than its endemic form, PF is rarely seen in adolescent groups. Glucocorticoids and other immunosuppressants are well-established treatments for pemphigus vulgaris (PV) and PF. In recent years, rituximab has been proven to be effective in the treatment of PV and PF. Nonetheless, the use of rituximab in the management of refractory juvenile PF is unclear. We report a case of successful treatment of recalcitrant juvenile PF with intravenous immunoglobulin (IVIG) and rituximab.
An 8-year-old boy presented in 2014 with scaly crusted lesions on the scalp for 2 months. On review of the past history, the patient had received multiple courses of antimicrobials and antifungals with the diagnosis of scalp impetigo and tinea capitis, respectively. Examination revealed erythematous scaly plaques over the scalp and face. Considering the working diagnosis of scalp psoriasis, the patient was started on acitretin. A skin biopsy done showed the presence of spongiotic dermatitis with eosinophilia. His skin lesions worsened rapidly over 2 months and he developed erythroderma with multiple erosions over the trunk and limbs without mucosal involvement. The clinical diagnosis was revised as PF and confirmed by a repeated skin biopsy which showed a spongiotic epidermis with subcorneal blisters [Figure 1]. Direct immunofluorescence showed the deposit of immunoglobulin G and C3 in the superficial intercellular space [Figure 2].
He was started on high-dose corticosteroids and immunosuppressants including cyclosporine and azathioprine between 2014 and 2015, which failed to induce clinical remission. He had multiple admissions for disease flares and secondary skin infections. At the age of 9 years old (end of 2015), he was started on a combination treatment of monthly IVIG (2 g/kg) and oral prednisolone 1 mg/kg/day. Since the disease activity was not in control, four doses of weekly rituximab 500 mg (375 mg/m2) were added in March 2016. Disease control was achieved with remission 4 weeks after starting rituximab. Subsequently, oral prednisolone was tapered off and IVIG was stopped. He was well with topical treatment alone until October 2017 when he experienced a disease flare. Another course of IVIG followed by rituximab was given. Oral prednisolone (0.5 mg/kg/day) was given concurrently. He went into partial remission after the IVIG and achieved complete remission only after the rituximab. Subsequently, he was on maintenance with oral methotrexate 10 mg/week and prednisolone 5 mg daily as the patient refused intravenous medications. Unfortunately, his disease was not under good control with a body surface area involvement of ≥90% [Figures 3 and 4]. In July 2020, he was started on the third cycle of rituximab followed by IVIG (2 g/kg). Intravenous methylprednisolone of 500 mg daily for 5 days was given concurrently during the first four cycles of IVIG. We managed to put his disease under control 4 months later with the combination treatments [Figures 5 and 6]. There were occasional scattered hyperkeratotic skin lesions that resolved with topical steroids. Since then, his disease was maintained with monotherapy of rituximab (500 mg for 4 weeks in April 2021, followed by a single dose of rituximab 500 mg every 6 months). He did not experience any adverse reactions during or after the treatment with IVIG and rituximab. [Flowchart 1] summarizes his disease control and systemic treatments between 2014 and 2021.
PF typically presents as subcorneal blisters that rupture easily to turn into scaly, crusted lesions in the seborrheic areas. There is no mucous membrane involvement in PF. These patients are frequently misdiagnosed as seborrheic dermatitis, psoriasis, or eczema. In our case, the patient presented with scaly, crusted lesions over the scalp and was initially treated as scalp psoriasis. With the disease progression, clinical diagnosis became more apparent, and the diagnosis was further confirmed by histopathology and immunofluorescence. Therefore, any patient presents with new-onset scaly or crusted lesions with or without blisters and erosion should be worked up to rule out autoimmune blistering disease.
Most juvenile PF patients can be treated with topical or systemic corticosteroids with or without immunosuppressants. Treatment of severe or refractory juvenile PF is not well established. There are only a few case reports on the treatment of rituximab in patients with juvenile PF, in which most of the case reports showed a good response to rituximab. These prove the potential efficacy of rituximab in refractory juvenile PF. Most of the reported cases showed long-term disease remission after 1–2 cycles of rituximab although some of the patients experienced disease flares 9–20 months later.
Most cases did not report any adverse reaction related to rituximab treatment. Nonetheless, life-threatening and fatal septicemia including bacterial septicemia and pneumonia had been reported, especially in those with concurrent immunosuppressants or in patients with an underlying malignancy. Previous studies reported an immunosuppressed period of 6–12 months after rituximab injections. Therefore, close monitoring and prompt treatment of septicemia are crucial. The usage of rituximab in juvenile PF should be reserved for refractory cases.
Most case reports on rituximab treatment in juvenile PF did not administer IVIG concurrently. A study by Ahmed et al. showed that combination therapy of rituximab and IVIG is effective in patients with refractory PV. Our patient successfully achieved clinical remission with this combination therapy. Systemic corticosteroid was given concurrently during the treatment course, and it may have a synergistic effect to induce disease remission.
We reported a case of refractory juvenile PF which showed a good response to the combination therapy of IVIG and rituximab. More studies are needed to determine the optimal treatment regime in refractory juvenile pemphigus diseases and their long-term safety profile.
Declaration of consent
The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
We would like to thank the Director General of the Ministry of Health, Malaysia, for his permission to publish this article.
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