Case Report: A successful treatment approach of rituximab and azathioprine for pemphigus vulgaris

Introduction

Pemphigus vulgaris (PV) is a grave autoimmune disorder characterised by blisters on the skin and mucous membranes. The root cause of this condition lies in the disruption of desmosomes, leading to a loss of adhesion among epidermal keratinocytes above the basal layer, resulting in flaccid blisters and erosions.¹ Pemphigus is classified as an autoimmune disease owing to the production of autoantibodies and the development of IgG and IgA reservoirs against desmosome components.² This condition typically affects individuals between the ages of 50 and 70, with children rarely affected by PV.³

The primary treatment options for PV include high-dose steroids and immunosuppressive medications, with rituximab being approved as an adjuvant medication.⁴ In India, the commonly used treatments are dexamethasone cyclophosphamide pulse therapy or oral corticosteroids with or without adjuvant immunosuppressants such as azathioprine, cyclophosphamide, mycophenolate mofetil, and cyclosporine. However, these medications can result in severe side effects, and many patients may succumb to treatment-related complications. Furthermore, some patients may not tolerate conventional treatments, which necessitates the use of alternative therapies.

Rituximab, a monoclonal antibody that targets the CD 20 antigen on the cell surface of B lymphocytes, is highly effective in treating pemphigus, particularly in cases of resistant disease or potentially fatal pemphigus.⁵ However, the high cost of this therapy compared to conventional options limits its use on a large scale in India.

Case report

Patient information

A 28-year-old male presented to the outpatient department complaining of fluid-filled lesions on his forehead and oral cavity, accompanied by burning pain and itching. The patient reported bursting the lesions, resulting in a clear fluid discharge. Over one-month, new fluid-filled lesions developed all over his face, followed by his upper limbs, trunk, and lower limbs. These lesions were associated with mild itching and pain and showed little tendency to heal (Figures 1 and 2).

Figure 1. Dark red Crusted lesions over the trunk.

Figure 2. Crusted lesions over the face.

The patient reported no significant medical, family, psychosocial, or genetic history. He is a farmer by occupation. Initially, he developed lesions on his forehead that spread to his cheek and back. He sought treatment from a private hospital, where he was prescribed oral and topical medications. However, after following this regimen for 4–5 months, the patient reported incomplete resolution of his symptoms. He subsequently consulted another private practitioner due to worsening symptoms and the development of ulcers in his oral cavity, making it difficult for him to consume spicy foods.

The practitioner prescribed a course of oral antibiotic minocycline 100 mg twice daily and referred the patient to a tertiary care hospital for further treatment. The underlying cause of the patient’s symptoms must be identified and treated appropriately to prevent further complications.

Discussion

PV is a severe and potentially life-threatening autoimmune disease. It can be fatal due to the loss of the epidermal barrier and body fluids, leading to subsequent infections. Therefore, PV must be diagnosed early and treated promptly to prevent fatal consequences. For a clinical diagnosis confirmation, histopathological analysis is required.⁶

The cornerstone of treatment for PV is systemic steroids, either with or without immunosuppression. However, some individuals may require higher doses of corticosteroids that can be unacceptable and difficult to manage. Unfortunately, we sometimes cannot reduce their high doses of drugs or provide treatment to those suffering from extreme cases.⁷

There are potential side effects linked with using rituximab. Seven patients had good drug tolerance and no adverse effects.⁵ Two individuals experienced angioedema, an acute side effect identified two hours after the infusion, and one patient required stopping of infusion. In contrast to earlier reports,⁵ the effects were seen during the second infusion. The second infusion was mainly uncomplicated, with the exception of one patient who experienced a slight infusion reaction during her initial infusion. Following rituximab infusion, sepsis occurred in two individuals (20%); they received the proper antibiotic treatment. Sepsis was experienced by patient number seven two weeks after beginning therapy. Acinetobacter was isolated from the blood on two separate occasions. Patient number eight developed sepsis after one week of initiating treatment, and the blood culture showed the growth of Staphylococcus aureus. The proper intravenous antibiotics were administered to both patients. Patient number seven made a full recovery. However, patient eight died because of sepsis. We recommended that rituximab be administered under close observation and in a setting with access to resuscitation equipment in case of infusion reactions. Sepsis is the most common side effect in patients with eroding skin, which serves as a portal of entry for organisms, including concurrent immunosuppressive medications. Sepsis is the most frequent cause of mortality in pemphigus.⁸ Strict clinical attention is necessary to identify sepsis early on, and efficient therapies are essential.⁹

Rituximab has a manageable adverse reaction, which includes infrequent infusion reactions and a low risk of infection—very few reports of severe adverse reactions to rituximab infusions.¹⁰ The injection rituximab received by our patient was well tolerated.¹¹

Conclusion

Pemphigus is a prevalent and potentially lethal organ-specific autoimmune disease arising from the production of autoantibodies targeting keratinocyte proteins. In cases where conventional immunosuppressive medications and corticosteroids fail or when significant adverse effects occur, rituximab may be an effective therapeutic regimen for pemphigus vulgaris (PV). Clinicians must remain cognizant that prolonged treatment with rituximab may result in positive outcomes. Furthermore, the response to rituximab treatment in pemphigus patients may be delayed. Nevertheless, clinicians should consider prolonged treatment with rituximab as it can yield favourable results in individuals suffering from pemphigus.

Authors contributions

All the authors have read and agreed to the final manuscript.