Approach Considerations

No therapy consistently improves multicentric reticulohistiocytosis (MRH). After an average course of 7-8 years, MRH often goes into remission, but considerable joint destruction may have already occurred. Many different drugs have been used in MRH, but patient response to therapy is difficult to determine because of the rarity of the disease, lack of controlled studies, and tendency for the remission to complicate evaluation of treatment efficacy.

Depending on its severity, MRH may limit activity. Physical therapy may prevent deformities and relieve symptoms.

Consultations with dermatologists and rheumatologists may be necessary. If internal malignancy occurs, consult with oncologists or surgeons as needed.

Patients with MRH should be monitored at regular intervals to track the activity of the disease and response to therapy.

Medical Care

Although no consistently effective treatment is known for MRH, the associated arthritis may respond to therapy with nonsteroidal anti-inflammatory drugs (NSAIDs).

Systemic corticosteroids, such as prednisone, and/or cytotoxic agents, particularly cyclophosphamide,^{[6, 7]} chlorambucil,^[6] and methotrexate,^{[8, 9, 7, 10]} may also affect the inflammatory response, as well as prevent further joint destruction and cause skin lesions to regress. Azathioprine^{[13, 14]} and cyclosporine^[15] are also reportedly effective in MRH.

Individual patients have reportedly responded to treatment with alendronate and other bisphosphonates.^{[16, 17]} Antimalarials have also been used in MRH.

Several reports have suggested that combining methotrexate with a tumor necrosis factor (TNF) ̶ alpha antagonist—such as etanercept, infliximab, or adalimumab—is more effective than the use of either alone.^{[11, 12, 18, 19, 20, 21]}

Tocilizumab, an interleukin-6 (IL-6) receptor inhibitor, reportedly caused remission of cutaneous and articular symptoms in a 35-year-old woman whose MRH was refractory to a combination of prednisone and methotrexate.^[27]

Surgical Care

Joint replacement may improve function in patients with burned-out disease that has resulted in deformity. Recently, a case of mutilating arthritis of the small joints of the hands due to MRH was reported as having been successfully managed with arthrodesis of the metacarpophalangeal joints.^[61]

In the case of internal malignancies, adequate tumor removal may result in the resolution of histiocytosis.^[39]

Mahajan et al reported on the case of a patient with MRH in whom confluent, disfiguring papules on the scalp, forehead, nasolabial folds, retroauricular region, and chin were successfully treated with carbon dioxide laser therapy. According to the authors, complete ablation was achieved, with no recurrence seen over an 8-month follow-up period.^[28]

Medication

Sroa N, Zirwas MJ, Bechtel M. Multicentric reticulohistiocytosis: A case report and review of the literature. Cutis. 2010 Mar. 85(3):153-5. [QxMD MEDLINE Link].
Selmi C, Greenspan A, Huntley A, Gershwin ME. Multicentric reticulohistiocytosis: a critical review. Curr Rheumatol Rep. 2015 Jun. 17 (6):511. [QxMD MEDLINE Link].
Luz FB, Gaspar AP, Ramos-e-Silva M, et al. Immunohistochemical profile of multicentric reticulohistiocytosis. Skinmed. 2005 Mar-Apr. 4(2):71-7. [QxMD MEDLINE Link].
Tashiro A, Takeuchi S, Nakahara T, Oba J, Tsujita J, Fukushi J, et al. Aberrant expression of CD10 in ground-glass-like multinucleated giant cells of multicentric reticulohistiocytosis. J Dermatol. 2010 Nov. 37(11):995-7. [QxMD MEDLINE Link].
Kroot EJ, Weel AE, Hazes JM, Zondervan PE, Heijboer MP, van Daele PL, et al. Diagnostic value of blind synovial biopsy in clinical practice. Rheumatology (Oxford). 2006 Feb. 45(2):192-5. [QxMD MEDLINE Link].
Ginsburg WW, O'Duffy JD, Morris JL, Huston KA. Multicentric reticulohistiocytosis: response to alkylating agents in six patients. Ann Intern Med. 1989 Sep 1. 111(5):384-8. [QxMD MEDLINE Link].
Liang GC, Granston AS. Complete remission of multicentric reticulohistiocytosis with combination therapy of steroid, cyclophosphamide, and low-dose pulse methotrexate. Case report, review of the literature, and proposal for treatment. Arthritis Rheum. 1996 Jan. 39(1):171-4. [QxMD MEDLINE Link].
Franck N, Amor B, Ayral X, et al. Multicentric reticulohistiocytosis and methotrexate. J Am Acad Dermatol. 1995 Sep. 33(3):524-5. [QxMD MEDLINE Link].
Gourmelen O, Le Loet X, Fortier-Beaulieu M, et al. Methotrexate treatment of multicentric reticulohistiocytosis. J Rheumatol. 1991 Apr. 18(4):627-8. [QxMD MEDLINE Link].
Rentsch JL, Martin EM, Harrison LC, Wicks IP. Prolonged response of multicentric reticulohistiocytosis to low dose methotrexate. J Rheumatol. 1998 May. 25(5):1012-5. [QxMD MEDLINE Link].
Kovach BT, Calamia KT, Walsh JS, Ginsburg WW. Treatment of multicentric reticulohistiocytosis with etanercept. Arch Dermatol. 2004 Aug. 140(8):919-21. [QxMD MEDLINE Link].
Lovelace K, Loyd A, Adelson D, Crowson N, Taylor JR, Cornelison R. Etanercept and the treatment of multicentric reticulohistiocytosis. Arch Dermatol. 2005 Sep. 141(9):1167-8. [QxMD MEDLINE Link].
Rudd A, Dolianitis C, Varigos G, Howard A. A case of multicentric reticulohistiocytosis responsive to azathioprine in a patient with no underlying malignancy. Australas J Dermatol. 2011 Nov. 52(4):292-4. [QxMD MEDLINE Link].
Hiramanek N, Kossard S, Barnetson RS. Multicentric reticulohistiocytosis presenting with a rash and arthralgia. Australas J Dermatol. 2002 May. 43(2):136-9. [QxMD MEDLINE Link].
Saito K, Fujii K, Awazu Y, et al. A case of systemic lupus erythematosus complicated with multicentric reticulohistiocytosis (MRH): successful treatment of MRH and lupus nephritis with cyclosporin A. Lupus. 2001. 10(2):129-32. [QxMD MEDLINE Link].
Goto H, Inaba M, Kobayashi K, et al. Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes. Arthritis Rheum. 2003 Dec. 48(12):3538-41. [QxMD MEDLINE Link].
Satoh M, Oyama N, Yamada H, Nakamura K, Kaneko F. Treatment trial of multicentric reticulohistiocytosis with a combination of predonisolone, methotrexate and alendronate. J Dermatol. 2008 Mar. 35(3):168-71. [QxMD MEDLINE Link].
Sellam J, Deslandre CJ, Dubreuil F, Arfi S, Kahan A. Refractory multicentric reticulohistiocytosis treated by infliximab: two cases. Clin Exp Rheumatol. 2005 Jan-Feb. 23(1):97-9. [QxMD MEDLINE Link].
Kalajian AH, Callen JP. Multicentric reticulohistiocytosis successfully treated with infliximab: an illustrative case and evaluation of cytokine expression supporting anti-tumor necrosis factor therapy. Arch Dermatol. 2008 Oct. 144(10):1360-6. [QxMD MEDLINE Link].
Yeter KC, Arkfeld DG. Treatment of multicentric reticulohistiocytosis with adalimumab, minocycline, methotrexate. Int J Rheum Dis. 2013 Feb. 16(1):105-6. [QxMD MEDLINE Link].
De Knop KJ, Aerts NE, Ebo DG, Van Offel JF, Stevens WJ, De Clerck LS. Multicentric reticulohistiocytosis associated arthritis responding to anti-TNF and methotrexate. Acta Clin Belg. 2011 Jan-Feb. 66(1):66-9. [QxMD MEDLINE Link].
Cash JM, Tyree J, Recht M. Severe multicentric reticulohistiocytosis: disease stabilization achieved with methotrexate and hydroxychloroquine. J Rheumatol. 1997 Nov. 24(11):2250-3. [QxMD MEDLINE Link].
Lonsdale-Eccles AA, Haworth AE, McCrae FC, Young-Min SA. Successful treatment of multicentric reticulohistiocytosis with leflunomide. Br J Dermatol. 2009 Aug. 161(2):470-2. [QxMD MEDLINE Link].
Shannon SE, Schumacher HR, Self S, Brown AN. Multicentric reticulohistiocytosis responding to tumor necrosis factor-alpha inhibition in a renal transplant patient. J Rheumatol. 2005 Mar. 32(3):565-7. [QxMD MEDLINE Link].
Broadwell AW, Calamia KT, Kransdorf MJ, Ginsburg WW. Healing of erosive disease in multicentric reticulohistiocytosis. J Rheumatol. 2010 Jun. 37(6):1366-7. [QxMD MEDLINE Link].
Mavragani CP, Batziou K, Aroni K, Pikazis D, Manoussakis MN. Alleviation of polyarticular syndrome in multicentric reticulohistiocytosis with intravenous zoledronate. Ann Rheum Dis. 2005 Oct. 64(10):1521-2. [QxMD MEDLINE Link]. [Full Text].
Pacheco-Tena C, Reyes-Cordero G, Ochoa-Albíztegui R, Ríos-Barrera V, González-Chávez SA. Treatment of multicentric reticulohistiocytosis with tocilizumab. J Clin Rheumatol. 2013 Aug. 19(5):272-6. [QxMD MEDLINE Link].
Mahajan RS, Shah AC, Nagar A, Freny BE. Treatment of facial lesions of multicentric reticulohistiocytosis by carbon dioxide laser. J Cutan Aesthet Surg. 2013 Jul. 6(3):161-3. [QxMD MEDLINE Link]. [Full Text].
Lotti T, Santucci M, Casigliani R, Fabbri P, Bondi R, Panconesi E. Multicentric reticulohistiocytosis. Report of three cases with the evaluation of tissue proteinase activity. Am J Dermatopathol. 1988 Dec. 10(6):497-504. [QxMD MEDLINE Link].
Gorman JD, Danning C, Schumacher HR, Klippel JH, Davis JC Jr. Multicentric reticulohistiocytosis: case report with immunohistochemical analysis and literature review. Arthritis Rheum. 2000 Apr. 43(4):930-8. [QxMD MEDLINE Link].
Nakamura H, Yoshino S, Shiga H, Tanaka H, Katsumata S. A case of spontaneous femoral neck fracture associated with multicentric reticulohistiocytosis: oversecretion of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by affected synovial cells. Arthritis Rheum. 1997 Dec. 40(12):2266-70. [QxMD MEDLINE Link].
Iwata H, Okumura Y, Seishima M, Aoyama Y. Overexpression of monocyte chemoattractant protein-1 in the overlying epidermis of multicentric reticulohistiocytosis lesions: a case report. Int J Dermatol. 2012 Apr. 51(4):492-4. [QxMD MEDLINE Link].
Adamopoulos IE, Wordsworth PB, Edwards JR, Ferguson DJ, Athanasou NA. Osteoclast differentiation and bone resorption in multicentric reticulohistiocytosis. Hum Pathol. 2006. 37(9):1176–85.
Islam AD, Naguwa SM, Cheema GS, Hunter JC, Gershwin ME. Multicentric reticulohistiocytosis: A rare yet challenging disease. Clin Rev Allergy Immunol. 2013 Feb 17.
Valencia IC, Colsky A, Berman B. Multicentric reticulohistiocytosis associated with recurrent breast carcinoma. J Am Acad Dermatol. 1998 Nov. 39(5 Pt 2):864-6. [QxMD MEDLINE Link].
Hotta M, Minamimoto R, Suzuki D, Takahashi A. Multicentric Reticulohistiocytosis Mimicking Malignancy on 18F-FDG PET/CT. Clin Nucl Med. 2017 Jul. 42 (7):567-568. [QxMD MEDLINE Link].
Tan BH, Barry CI, Wick MR, et al. Multicentric reticulohistiocytosis and urologic carcinomas: a possible paraneoplastic association. J Cutan Pathol. 2011 Jan. 38(1):43-8. [QxMD MEDLINE Link].
Han L, Huang Q, Liao KH, et al. Multicentric reticulohistiocytosis associated with liver carcinoma: report of a case. Case Rep Dermatol. 2012 May. 4(2):163-9. [QxMD MEDLINE Link]. [Full Text].
El-Haddad B, Hammoud D, Shaver T, Shahouri S. Malignancy-associated multicentric reticulohistiocytosis. Rheumatol Int. 2011 Sep. 31(9):1235-8. [QxMD MEDLINE Link].
Kishikawa T, Miyashita T, Fujiwara E, Shimomura O, Yasuhi I, Niino D, et al. Multicentric reticulohistiocytosis associated with ovarian cancer. Mod Rheumatol. 2007. 17(5):422-5. [QxMD MEDLINE Link].
Huang X, Zhang L, Zhang S. Multicentric reticulohistiocytosis with extra-mammillary Paget's disease: a case report. Eur J Med Res. 2013 Oct 29. 18(1):38. [QxMD MEDLINE Link].
Rudha Y, Starobinska E, Abdulqader Y, Attya A, Guerrero C, Parperis K. Multicentric reticulohistiocytosis associated with thymic carcinoma. Rheumatology (Oxford). 2017 Oct 1. 56 (10):1706. [QxMD MEDLINE Link].
Tariq S, Hugenberg ST, Hirano-Ali SA, Tariq H. Multicentric reticulohistiocytosis (MRH): case report with review of literature between 1991 and 2014 with in depth analysis of various treatment regimens and outcomes. Springerplus. 2016. 5:180. [QxMD MEDLINE Link]. [Full Text].
West KL, Sporn T, Puri PK. Multicentric reticulohistiocytosis: a unique case with pulmonary fibrosis. Arch Dermatol. 2012 Feb. 148(2):228-32. [QxMD MEDLINE Link].
Webb-Detiege T, Sasken H, Kaur P. Infiltration of histiocytes and multinucleated giant cells in the myocardium of a patient with multicentric reticulohistiocytosis. J Clin Rheumatol. 2009 Feb. 15(1):25-6. [QxMD MEDLINE Link].
Benucci M, Sulla A, Manfredi M. Cardiac engagement in multicentric reticulohistiocytosis: report of a case with fatal outcome and literature review. Intern Emerg Med. 2008 Jun. 3(2):165-8. [QxMD MEDLINE Link].
Lambert CM, Nuki G. Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy. Ann Rheum Dis. 1992 Jun. 51(6):815-7. [QxMD MEDLINE Link]. [Full Text].
Fast A. Cardiopulmonary complications in multicentric reticulohistiocytosis. Report of a case. Arch Dermatol. 1976 Aug. 112(8):1139-41. [QxMD MEDLINE Link].
Yang HJ, Ding YQ, Deng YJ. Multicentric reticulohistiocytosis with lungs and liver involved. Clin Exp Dermatol. 2009 Mar. 34(2):183-5. [QxMD MEDLINE Link].
Taniguchi T, Asano Y, Okada A, Sugaya M, Sato S. Ultraviolet light-induced Köbner phenomenon contributes to the development of skin eruptions in multicentric reticulohistiocytosis. Acta Derm Venereol. 2011 Mar. 91(2):160-3. [QxMD MEDLINE Link].
Fett N, Liu RH. Multicentric reticulohistiocytosis with dermatomyositis-like features: a more common disease presentation than previously thought. Dermatology. 2011. 222(2):102-8. [QxMD MEDLINE Link].
Mun JH, Ko HC, Kim MB. Multicentric reticulohistiocytosis masquerading as dermatomyositis: similar and different features. J Dermatol. 2012 Jan. 39(1):104-7. [QxMD MEDLINE Link].
Bennassar A, Mas A, Guilabert A, Julia M, Mascaro-Galy JM, Herrero C. Multicentric reticulohistiocytosis with elevated cytokine serum levels. J Dermatol. 2011 Sep. 38(9):905-10. [QxMD MEDLINE Link].
Shima N, Murosaki T, Nagashima T, Iwamoto M, Amano Y, Nakano N, et al. Multicentric Reticulohistiocytosis with Dermatomyositis-like Eruptions. Intern Med. 2017. 56 (15):2063-2066. [QxMD MEDLINE Link]. [Full Text].
Wat M, Sun GS, Rodriguez-Waitkus PM, Hsu S. Granuloma annulare mimicking multicentric reticulohistiocytosis. Dermatol Online J. 2013 Nov 15. 19(11):20400. [QxMD MEDLINE Link].
Yamada T, Kurohori YN, Kashiwazaki S, Fujibayashi M, Ohkawa T. MRI of multicentric reticulohistiocytosis. J Comput Assist Tomogr. 1996 Sep-Oct. 20(5):838-40. [QxMD MEDLINE Link].
Kamel H, Gibson G, Cassidy M. Case report: the CT demonstration of soft tissue involvement in multicentric reticulohistiocytosis. Clin Radiol. 1996 Jun. 51(6):440-1. [QxMD MEDLINE Link].
Asano T, Suzutani K, Watanabe A, Honda A, Mori N, Yashiro M, et al. The utility of FDG-PET/CT imaging in the evaluation of multicentric reticulohistiocytosis: A case report. Medicine (Baltimore). 2018 Aug. 97 (33):e11449. [QxMD MEDLINE Link]. [Full Text].
Zhang B, Zhou H, Han J, Shi X, Zhang X. 18F-FDG PET/CT Findings in Multicentric Reticulohistiocytosis. Clin Nucl Med. 2016 Apr. 41 (4):333-5. [QxMD MEDLINE Link].
Farokhi A, van Vugt RM, Hoekzema R, Nurmohamed MT. Multicentric reticulohistiocytosis: a case report. BMC Res Notes. 2018 Sep 4. 11 (1):647. [QxMD MEDLINE Link]. [Full Text].
Wade RG, Daivajna S, Chapman P, Murphy JG, Makkuni D. Hand surgery for Multicentric Reticulohistiocytosis: A new avenue of treatment and review of the literature. Int J Surg Case Rep. 2013. 4(8):744-7. [QxMD MEDLINE Link]. [Full Text].
Motegi S, Yonemoto Y, Yanagisawa S, Toki S, Uchiyama A, Yamada K, et al. Successful Treatment of Multicentric Reticulohistiocytosis with Adalimumab, Prednisolone and Methotrexate. Acta Derm Venereol. 2016 Jan. 96 (1):124-5. [QxMD MEDLINE Link].
Macía-Villa CC, Zea-Mendoza A. Multicentric reticulohistiocytosis: case report with response to infliximab and review of treatment options. Clin Rheumatol. 2016 Feb. 35 (2):527-34. [QxMD MEDLINE Link].

Media Gallery

Multiple erythematous nodules are present on the dorsal hands of this adolescent with an inflammatory arthropathy.
Multiple erythematous to brown nodules on the fingers.
Erythematous, poikilodermatous, mamillated plaque on the anterior chest.
Histopathology of multicentric reticulohistiocytosis (MRH) skin lesions.
Histopathology of multicentric reticulohistiocytosis (MRH) skin lesions. Higher power demonstrating multinucleated giant cells with eosinophilic ground-glass cytoplasm.
Erythematous to brown papules overlying the right dorsal hand and wrist and erythematous to violaceous patches over the right dorsal hand and fingers. The cutaneous changes are in a photodistributed pattern and mimic the changes of dermatomyositis.
Erythematous to brown papules and erythematous to violaceous patches overlying the right dorsal hand and fingers, with a crusted erosion overlying the fourth metacarpophalangeal joint. These cutaneous changes can be easily confused with dermatomyositis.
Nodules on a hand with deformed joints from arthritis due to multicentric reticulohistiocytosis.
Swollen elbow and nodules on the forearm.
Cobblestone papules on the eyelid and papules on the forehead.
Low-power view of a biopsy sample of large histiocytes and multinucleated giant cells in the dermis.
High-power view of large histiocytes in the dermis.
Brown immunoperoxidase staining for lysozyme in histiocytes.

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Author

Alisa N Femia, MD Assistant Professor, Ronald O Perelman Department of Dermatology, New York University Medical Center

Alisa N Femia, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Medical Dermatology Society, Rheumatologic Dermatology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Ruth Ann Vleugels, MD, MPH Assistant Professor of Dermatology, Harvard Medical School; Associate Physician, Department of Dermatology, Brigham and Women's Hospital; Associate Physician, Department of Immunology and Allergy, Children's Hospital Boston

Ruth Ann Vleugels, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Rheumatology, American Medical Association, Society for Investigative Dermatology, Medical Dermatology Society, Dermatology Foundation

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Genentech as a consultant for a potential study on a drug that has yet to be approved for any use<br/>Received honoraria from UpToDate for author/editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for these trust accounts; I served on a safety monitoring committee for Principia Biopharma (ended 9-2021) for: Stocks held in various trust accounts: Allergen; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen; Gilead.

Ronald P Rapini, MD Professor and Chair, Department of Dermatology, The University of Texas MD Anderson Cancer Center; Distinguished Chernosky Professor and Chair of Dermatology, Professor of Pathology, University of Texas McGovern Medical School at Houston

Ronald P Rapini, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, American Society of Dermatopathology, Association of Professors of Dermatology, Society for Investigative Dermatology, Texas Dermatological Society

Disclosure: Book royalties from Elsevier publishers.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rosalie Elenitsas, MD Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology

Disclosure: Lippincott Williams Wilkins Royalty Textbook editor

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology