Background Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis. It can affect any organ but predominantly skin and joints. Joint involvement usually precedes skin involvement and can be very destructive. Early diagnosis and treatment is therefore important but can be difficult.We describe a woman with MRH and severe erosive joint disease who responded to combination tocilizumab and zoledronate.
Objectives A 43 yr old woman presented in 2012 with a 3 mth history of rash on her face, chest and ears and fingers, and arthralgia affecting shoulders, wrists, fingers and knees. On examination she had diffuse hand swelling, right knee effusion and erythematous eruption affecting her face, chest and ears with papules on the sides of her fingers.
Investigations: normal FBC, CRP, U+Es, LFTs. ESR 12 mm/hr. ANA +ve at 1:1280 (finely speckled). Ro +ve; ENA including Jo-1, ANCA and dsDNA antibodies -ve, C3/4, Igs all normal/-ve. Hand XR: periarticular DIP erosions. Skin biopsy: large multinucleate cells with abundant cytoplasm staining positive with CD68 (histiocytic marker); CD1a negative (Langerhans cell marker), consistent with MRH. PET-CT body: incidental finding of thymic remnant.
Methods Initial Rx:prednisolone 20 mg od + HCQ 200mg bd with initial good response of joint and skin symptoms, but recurrence of symptoms on reducing steroid dose. Nov 2012: MTX up to 20mg /week added. Stopped after 4 mths because of a linear rise in P3NP levels to 11.2. Fibroscan showed slightly raised stiffness of 7.4kPa. AZA 75mg od introduced in Feb 2013, then etanercept 50mg weekly. This led to good control of symptoms for approximately 4 mths on single agent therapy. March 2014: relapse of joint and skin symptoms. June 2014: tocilizumab 8mg/kg iv 4 weekly started. After 5 infusions, her skin cleared for the first time. December 2014: relapse of joint and skin symptoms. Tocilizumab was adjusted to 650mg per mth from 620mg in view of slight weight gain. Annual iv zoledronate 5mg was started. She has had no further joint or skin exacerbations. July 2015: prednisolone was down to 1mg daily and stopped completely by May 2016. From July 2015 there appears to have been no progression in DIP joint erosions, and possibly some healing of the DIP changes. She has remained off any steroids.
Conclusions The pathogenesis of MRH is poorly understood. The overexpression of cytokines including TNFα, IL-1 and IL-6 in inflammatory lesions gives a number of logical drug options, including tocilizumab. The observation that mononuclear cells in both skin nodules and synovium in MRH exhibit some properties of osteoclasts might explain the mechanism behind reported success using bisphosphonates. To our knowledge, this is only the second case to report success with using tocilizumab in the treatment of MRH and the first to report on concomitant treatment with a bisphosphonate. No adverse effects have been observed throughout treatment, and remission appears to be sustained. Without withdrawing treatment we cannot know if the remission is natural or drug induced, though the relatively short timescale suggests a drug effect.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.