Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 3609  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (1,236 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 :: Introduction
 :: Case Report
 :: Discussion
 ::  References
 ::  Article Figures

 Article Access Statistics
    PDF Downloaded25    
    Comments [Add]    
    Cited by others 3    

Recommend this journal


  Table of Contents     
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

1 Cancer Center and Blood Institute, Idaho, United States, USA
2 Pathology, St. Joseph Regional Medical Center, Idaho, USA

Date of Web Publication5-Nov-2014

Correspondence Address:
Dr. B K Shah
Cancer Center and Blood Institute, Idaho, United States
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0022-3859.143975

Rights and Permissions

 :: Abstract 

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 2023 Jun 6];60:406-8. Available from:

 :: Introduction Top

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 Top

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 Top

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.

 :: References Top

Cyr PR. Diagnosis and management of granuloma annulare. Am Fam Physician 2006;74:1729-34.  Back to cited text no. 1
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.  Back to cited text no. 2
Brodell RT, Stratman E, Ofori AO. Granuloma annulare. In: Basow DS, editor. Up To DateWaltham, Massachusetts: UpToDate; 2013. Updated 2014 Mar 31.  Back to cited text no. 3
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.  Back to cited text no. 4
Cephalon, Inc. Treanda ® (Bendamustine Hydrochloride) for Injection 2012. Prescribing Information. Available from: [Last accessed on 21 Sept 2013].  Back to cited text no. 5
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.  Back to cited text no. 6
Carlin MC, Ratz JL. A case of generalized granuloma annulare responding to hydroxychloroquine. Cleve Clin J Med 1987;54:229-32.  Back to cited text no. 7
Biogen Idec, Inc. and Genentech, Inc. Rituxan® (Rituximab) for Injection 2013. Prescribing Information. Available from: [Last accessed on 21 Sept 2013].  Back to cited text no. 8
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.  Back to cited text no. 9
Semple JW. Rituximab disciplines T cells, spares platelets. Blood 2007;110:2784-5.  Back to cited text no. 10
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.  Back to cited text no. 11
Liossis SN, Sfikakis PP. Rituximab-induced B cell depletion in autoimmune diseases: Potential effects on T cells. Clin Immunol 2008;127:280-5.  Back to cited text no. 12
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.  Back to cited text no. 13


  [Figure 1], [Figure 2]

This article has been cited by
1 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]
2 Complete remission of disseminated granulomatous dermatitis related to chronic eosinophilic leukemia following allogeneic stem cell transplantation
Yan Beauverd, Begonia Cortés, Isabelle Masouye, Yves Chalandon
Leukemia & Lymphoma. 2017; 58(2): 470
[Pubmed] | [DOI]
3 The continuing evolution of targeted therapy for inflammatory skin disease
C. Schlapbach,A. A. Navarini
Seminars in Immunopathology. 2016; 38(1): 123
[Pubmed] | [DOI]


Print this article  Email this article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow