Journal of Postgraduate Medicine
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Year : 2014  |  Volume : 60  |  Issue : 4  |  Page : 406-408  

Resolution of granuloma annulare following treatment with bendamustine and rituximab in a patient with follicular lymphoma: A serendipitous finding

BK Shah1, Y Hewett1, A Peterson2, D Tretheway2,  
1 Cancer Center and Blood Institute, Idaho, United States, USA
2 Pathology, St. Joseph Regional Medical Center, Idaho, USA

Correspondence Address:
Dr. B K Shah
Cancer Center and Blood Institute, Idaho, United States


Granuloma annulare is a benign inflammatory dermatosis. Cell-mediated immunity and delayed hypersensitivity are proposed pathogenic mechanisms. We report in this paper a case of generalized granuloma annulare that resolved after the patient was treated with rituximab and bendamustine for stage IV follicular lymphoma.

How to cite this article:
Shah B K, Hewett Y, Peterson A, Tretheway D. Resolution of granuloma annulare following treatment with bendamustine and rituximab in a patient with follicular lymphoma: A serendipitous finding.J Postgrad Med 2014;60:406-408

How to cite this URL:
Shah B K, Hewett Y, Peterson A, Tretheway D. Resolution of granuloma annulare following treatment with bendamustine and rituximab in a patient with follicular lymphoma: A serendipitous finding. J Postgrad Med [serial online] 2014 [cited 2023 Mar 27 ];60:406-408
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Full Text


Granuloma annulare (GA) is characterized by annular skin lesions, which may be localized or disseminated. [1] We report a case of GA that resolved after treatment of follicular lymphoma with rituximab and bendamustine.

 Case Report

A 74-year-old female presented to the hematology clinic for evaluation and management of chronic leukopenia. The patient denied any fever, change in appetite, weight loss or night sweats. Her past medical history was significant for a three-year history of biopsy-proven steroid refractory generalized interstitial granuloma annulare (GA) [Figure 1] and [Figure 2].{Figure 1}{Figure 2}

Her physical examination showed blood pressure of 146/84, pulse 73/min, temperature 97.9F, respiratory rate 16/min, oxygen saturation 98% on room air and weight of 152 pounds. Skin examination revealed multiple hyperpigmented annular plaques consistent with GA on the upper extremities, axilla and bilateral inguinal regions. There were no palpable lymph nodes and no palpable liver or spleen.

Baseline laboratory data showed a white blood cell count 3500/μL, with 60% segmented neutrophils, 4% band neutrophils, and 27% lymphocytes. Hemoglobin was 14 g/dL, RBC 5.36 million/μL and platelet count 142,000/μL. Renal and hepatic functions were within normal limits. Computed tomography scan of chest, abdomen and pelvis revealed splenomegaly and axillary lymphadenopathy. The lymph node biopsy revealed a population of small lymphocytes, which expressed CD20, CD10, PAX5, BCL-2, and BCL-6 consistent with follicular lymphoma. Bone marrow aspiration and biopsy revealed involvement by follicular lymphoma.

Patient was started on treatment with immunochemotherapy with rituximab 375 mg/m 2 day 1 and bendamustine 100 mg/m 2 day 1, day 2 intravenously every four weekly. Just prior to the second cycle of treatment, the patient noted an improvement in her annular lesions. Six cycles of treatment were completed without incident.

Follow-up CT scan and bone marrow biopsy eleven weeks later were negative for any evidence of lymphoma. The patient remains lesion-free nine months following the completion of immunochemotherapy.


Although GA is usually benign and self-limiting in nature, it may persist for many years. The etiology is unclear, but the presence of helper T-cells in GA infiltrates suggests a T-cell mediated process. [2]

Treatments for localized forms of GA include topical steroids, calcineurin inhibitors, phototherapy or photochemotherapy [3] Hydroxychloroquine, isoretinoin, dapsone, fumaric acid, [4] or cyclosporine may be used for generalized GA with varying degrees of success.

It is unclear whether bendamustine or rituximab or the combination was responsible for the resolution of GA, but an argument could be made for either agent. Bendamustine is an alkylating agent approved for use in non-Hodgkin's lymphoma and chronic lymphocytic leukemia. [5] The immunosuppressive effects of alkylating agents on T cells have been documented. [6],[7]

Rituximab is a murine/human monoclonal antibody that binds specifically to the CD20 subunit on B lymphocytes. [8] It is approved for use in the treatment of non-Hodgkin's lymphoma, rheumatoid arthritis and Wegener's granulomatosis. It is also used off-label for a variety of diseases, including immune thrombocytopenia purpura, autoimmune hemolytic anemia, lupus, primary sicca syndrome, dermatomyositis, ANCA-positive vasculitis, cryoglobulinemia, pemphigus, Sjogren's syndrome, Waldenstrom's macroglobulinemia, and thrombotic thrombocytopenic purpura. [9] Although the effect of rituximab is B-cell-mediated, there is growing evidence that it may produce secondary effects in T cells as well. [10],[11],[12] The depletion of B cells by rituximab results in decreased antigen presentation to T cells, which in turn may enhance the numbers and function of regulatory T cells.

To the best of our knowledge, this is the first case report of resolution of generalized interstitial granuloma annulare following treatment with rituximab and bendamustine. Rituximab and (or) bendamustine may represent additional options for severe generalized GA not responding to common treatment modalities. However, these drugs are associated with several toxicities including but not limited to cytopenias, infections, nausea, weight loss, anorexia etc. [13] Therefore, risks and benefits should be carefully analyzed before using this combination for GA patients.


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