| Article Access Statistics|
| Viewed||3116 |
| Printed||108 |
| Emailed||0 |
| PDF Downloaded||25 |
| Comments ||[Add] |
| Cited by others ||2 |
Click on image for details.
|Year : 2014 | Volume
| 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
|Date of Web Publication||5-Nov-2014|
Dr. B K Shah
Cancer Center and Blood Institute, Idaho, United States
Source of Support: None, Conflict of Interest: None
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.
Keywords: Bendamustine, follicular lymphoma, granuloma annulare, non-Hodgkin lymphoma, immunochemotherapy, rituximab
|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;60:406-8
|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 2022 Jan 21];60:406-8. Available from: https://www.jpgmonline.com/text.asp?2014/60/4/406/143975
| :: Introduction|| |
Granuloma annulare (GA) is characterized by annular skin lesions, which may be localized or disseminated.  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: Interstitial infiltrate of lymphocytes and histiocytes with a few giant cells (multinucleated histiocytes) involving the mid dermis. The lesion disrupts dermal collagen, and has associated dermal mucin|
Click here to view
|Figure 2: Higher power photomicrograph showing interstitial lymphocyte, histiocytes and giant cells|
Click here to view
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.
| :: Discussion|| |
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. 
Treatments for localized forms of GA include topical steroids, calcineurin inhibitors, phototherapy or photochemotherapy  Hydroxychloroquine, isoretinoin, dapsone, fumaric acid,  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.  The immunosuppressive effects of alkylating agents on T cells have been documented. ,
Rituximab is a murine/human monoclonal antibody that binds specifically to the CD20 subunit on B lymphocytes.  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.  Although the effect of rituximab is B-cell-mediated, there is growing evidence that it may produce secondary effects in T cells as well. ,, 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.  Therefore, risks and benefits should be carefully analyzed before using this combination for GA patients.
| :: References|| |
Cyr PR. Diagnosis and management of granuloma annulare. Am Fam Physician 2006;74:1729-34.
Fayyazi A, Schweyer S, Eichmeyer B, Herms J, Hemmerlein B, Radzun HJ, et al.
Expression of IFNgamma, coexpression of TNFalpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare. Arch Dermatol Res 2000;292:384-90.
Brodell RT, Stratman E, Ofori AO. Granuloma annulare. In: Basow DS, editor. Up To DateWaltham, Massachusetts: UpToDate; 2013. Updated 2014 Mar 31.
Weber HO, Borelli C, Rocken M, Schaller M. Treatment of disseminated granuloma annulare with low-dose fumaric acid. Acta Derm Venereol 2009;89:295-8.
Klippstein A, Schneider CP, Sayer HG, Höffken K. Pneumocystis carinii pneumonis as a complication of bendamustine monotherapy in a patient with advanced progressive breast cancer. J Cancer Res Clin Oncol 2003;129:316-9.
Carlin MC, Ratz JL. A case of generalized granuloma annulare responding to hydroxychloroquine. Cleve Clin J Med 1987;54:229-32.
Sailler L. Rituximab off label use for difficult-to-treat auto-immune diseases: Reappraisal of benefits and risks. Clin Rev Allergy Immunol 2008;34:103-10.
Semple JW. Rituximab disciplines T cells, spares platelets. Blood 2007;110:2784-5.
Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, Portales-Pérez D, Baranda L, Abud-Mendoza C, et al.
Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: A pilot study. Arthritis Res Ther 2006;8:R83.
Liossis SN, Sfikakis PP. Rituximab-induced B cell depletion in autoimmune diseases: Potential effects on T cells. Clin Immunol 2008;127:280-5.
Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol 2014;93:403-9.
[Figure 1], [Figure 2]
|This article has been cited by|
||Granulome annulaire généralisé : étude anatomoclinique
| ||M. Ehret, C. Lenormand, J.-N. Scrivener, L. Gusdorf, D. Lipsker, B. Cribier |
| ||Annales de Dermatologie et de Vénéréologie. 2020; 147(4): 271 |
|[Pubmed] | [DOI]|
||The continuing evolution of targeted therapy for inflammatory skin disease
| ||C. Schlapbach,A. A. Navarini |
| ||Seminars in Immunopathology. 2016; 38(1): 123 |
|[Pubmed] | [DOI]|