Follicular Non-Hodgkin's Lymphoma with Refractory Paraneoplastic Pemphigus: Case Report with Review of Novel Treatment Modalities

Abstract

In this paper a patient with a non-Hodgkin's lymphoma (NHL) and paraneoplastic pemphigus (PNP) is described. PNP is a very rare, painful mucocutaneous intraepithelial blistering disease associated with occult or confirmed malignancy. Patients with PNP show severe, progressive mucocutaneous disease with a high mortality rate, because of drug-induced infectious complications. The patients sometimes benefit from high doses of oral corticosteroids. However, pulse therapy with high doses of prednisolone (or dexamethasone) in combination with other immunosuppressants induces variable and inconstant results. Intravenous immunoglobulin (IVIg) has been applied in different cases of PNP with encouraging results. Plasmapheresis or plasma exchange (PE) in combination with corticosteroids and/or cyclophosphamide or azathioprine showed similar rapid and beneficial results in association with decreasing auto-antibody levels in this group of refractory pemphigus. Another interesting therapeutic option is rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B-lymphocytes. Administration of rituximab for patients with PNP in combination with follicular NHL is not always successful regarding oral lesions as we report in this case. PE leading to prompt depletion of autoreactive antibodies combined with immunosuppressants or synchronisation of PE with IVIg seems the best treatment modality for this refractory group, but the therapeutic value and appropriate timing of rituximab obviously deserve further evaluation in patients with low grade NHL and PNP.

Off-label uses of biologics in dermatology: Rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (Part 2 of 2)

“…Three case reports describe significant improvement in oral and cutaneous lesions after rituximab [30][31][32] ; however, one report describes only partial improvement 33 and two additional reports describe less successful results, especially with regard to mucosal lesions. 34,35 The mechanism of action in paraneoplastic pemphigus is likely similar to that in PV. In addition, most of the treated patients experienced at least partial remission of the underlying neoplasm, and this may have contributed to the observed improvement.…”

Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007

“…29,31 Paraneoplastic pemphigus carries a poor prognosis, with a 2 year 90% mortality rate. 29 Bullous pemphigoid is characterized by tense, subepidermal, blisters of the skin due to antibodies against basement membrane antigens, bullous pemphigoid antigens 1 and 2.…”

“…1 However, other infusion regimens have been described, including repeating a full cycle and/or monthly or every other week "X". 14,25,31 Concominant systemic therapy used during rituximab treatment have included prednisone, dexamethasone, mycophenolate mofetil, azathioprine, cyclophosphamide, colchicine, methotrexate, 41 IVIg, plasmaphoresis, 42 daclizumab (anti-CD25 antibody), 34 and immunoabsorption. 13 As noted earlier, in this review we found 69.01% of autoimmune blistering patients treated with rituximab showed a complete response and 25.35% showed partial response.…”

“…The fi rst reported use of rituximab was in a patient with follicular lymphoma-associated paraneoplastic pemphigus. 32 Thereafter, reports emerged of rituximab used in the treatment of pemphigus vulgaris, 5-7,9,10,12,14,17-27 pemphigus vegetans, 12 pemphigus foliaceus, 5,8,11,12,28 paraneoplastic pemphigus, [29][30][31][32][33] bullous pemphigoid, 34 and epidermolysis bullosa acquisita. 13,35,36 Most commonly, rituximab is administered as a cycle of weekly infusions of 375 mg/m 2 for four weeks.…”

“…14 In the previous studies of IVIg treatment for patients with pemphigus, it was reported that the autoantibody titers did reduce during the treatment. 16 Rituximab was originally developed to treat refractory, low-grade, follicular, B cell non-Hodgkins lymphoma 2 , but has been used experimentally in various autoimmune diseases including autoimmune blistering disorders (pemphigus vulgaris, 5-7,9-10,12,14,17-27 pemphigus vegetans, 12 pemphigus foliaceus, 5,8,11,12,28 paraneoplastic pemphigus, [29][30][31][32][33] bullous pemphigoid, 34 and epidermolysis bullosa acquisita 13,35,36 …”