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Table of Contents
Year : 2019  |  Volume : 37  |  Issue : 3  |  Page : 174-175

Papular xanthoma with destructive arthritis (a variant of multicentric reticulohistiocytosis): Reports of two cases

1 Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Dermatology, Cathay General Hospital, Taipei; Department of Dermatology, National Taiwan University Hospital HsinChu Branch, Hsinchu, Taiwan
3 Department of Dermatology, National Taiwan University Hospital; Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Date of Web Publication24-May-2019

Correspondence Address:
Dr. Tsen-Fang Tsai
Department of Dermatology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_15_18

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How to cite this article:
Sin CZ, Cheng YP, Tsai TF. Papular xanthoma with destructive arthritis (a variant of multicentric reticulohistiocytosis): Reports of two cases. Dermatol Sin 2019;37:174-5

How to cite this URL:
Sin CZ, Cheng YP, Tsai TF. Papular xanthoma with destructive arthritis (a variant of multicentric reticulohistiocytosis): Reports of two cases. Dermatol Sin [serial online] 2019 [cited 2023 Feb 4];37:174-5. Available from: https://www.dermsinica.org/text.asp?2019/37/3/174/259100

Dear Editor,

Multicentric reticulohistiocytosis (MRH) is a rare systemic inflammatory disease of uncertain etiology that presents clinically with cutaneous papulonodular lesions and erosive arthritis. MRH is characterized pathologically by multinucleated giant cells with characteristic ground-glass appearance of the eosinophilic cytoplasm with multiple organ involvement. Rare cases of MRH had been reported which showed abundant foamy histiocytes in the dermis without characteristic multinucleated giant cells. Here, we reported two cases who had clinical manifestations consistent with MRH, but showed xanthomatous changes histopathologically.

  Case Reports Top

Case 1

A 24-year-old female patient was otherwise healthy and presented with asymptomatic skin lesions for 10 years. Skin finding revealed crops of 1–4 mm, yellowish or erythematous papules on the forehead, nape, occipital scalp [Figure 1]a, and nail folds of bilateral hands, with characteristic “coral bead sign” appearance and swelling over the bilateral proximal interphalangeal joints [Figure 1]b. She also reported a 4-year history of polyarthralgia affecting the ankles, elbows, wrists, and interphalangeal joints. Radiograph of the bilateral hands disclosed acro-osteolysis of the right second distal phalanx [Figure 1]c. A skin biopsy of a left occipital papule demonstrated the presence of several vacuolated cells in the epidermis and some aggregates of foamy histiocytes in the upper dermis. Immunohistochemically, the histiocytes were positive for CD163 but negative for S100, CD1a, and cyclin D1. The patient's serum lipid profile was unremarkable, and no malignancy was identified on computed tomographic scan. She was treated with prednisolone 30 mg/day, with partial effects which were tapered slowly when adalimumab was added 3 months later.
Figure 1: (a) Crops of yellowish or erythematous papules on the occipital scalp and nape. (b) “Coral beads”-like lesions on the proximal nail folds and swelling over the bilateral proximal interphalangeal joints. (c) Erosive bone lesion of the right second distal phalanx. (d) Accumulation of large foamy cells in the upper dermis, with some vacuolated cells in the epidermis (H and E, ×200)

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Case 2

A 40-year-old female patient had previously been well and presented with progression of skin lesions for 5 months. Physical examinations disclosed several 2–4 mm painless, firm, yellow-to-erythematous papules on the forehead, nasolabial folds, temporal scalp, and periungual region of hands. A biopsy specimen of one of the periungual papules was obtained which revealed hyperkeratosis and accumulation of large cells with eccentric nuclei and abundant foamy-to-clear cytoplasm in the upper dermis, with some vacuolated cells also seen in the epidermis [Figure 1]d. The infiltrating cells in the dermis were diffusely immunoreactive for CD68 and negative for cytokeratin and S100, consistent with a xanthomatous lesion. A comprehensive metabolic panel, including lipid profile, was unremarkable. The patient started treatment with oral doxycycline 200 mg per day for 2 months without effects, and she eventually lost to follow-up. During the following years, polyarthritis developed over the hands, and she received treatment with adalimumab in another medical facility. The cutaneous lesions disappeared gradually and the polyarthritis was improved.

The first confirmed case of MRH with systemic manifestations was reported in 1937.[1] Skin is regarded as the most feasible site for pathologic examination, which demonstrates lymphocytes and histiocytes infiltrated in the dermis in the early lesions, whereas the late lesions present with pathognomonic findings as diffuse dermal infiltration of multinucleated giant cells with eosinophilic ground-glass appearance.[2] However, cases with typical clinical and radiographic features but with atypical xanthomatous histopathological presentations had been reported first in 1946 by Graham and Stansfeld in a 20-year-old male.[3] Other than skin, acumination of foamy, vacuolated cells had also been detected in synovial membrane.[4] However, these features were seldom noticed until 2009 when Matiz et al. reported another case of a 3-year-old girl who presented with similar clinical and pathological features and some foamy, vacuolated cells were also present in the overlying epidermis. Her skin eruptions had excellent response to infliximab; however, the synovitis was not improved.[5] In 2013, another 32-year-old Filipina woman was examined who had similar clinical presentations and histological findings, whose skin lesions had partial response to corticosteroid and methotrexate, but her arthritis and joint deformity remained unresponsive.[6] Besides, one similar case with double cancers had been reported recently.[7] Our two cases were very similar to the recent three reported cases which also showed the accumulation of dermal foamy histiocytes and some cells with clear, vacuolated cytoplasm in the epidermis. Adalimumab is a tumor necrosis factor-alpha (TNF-α) blocker and has been used successfully in the treatment of many inflammatory arthritis, including MRH. The mechanism of adalimumab in MRH is not well described. However, it has been reported that TNF-α-positive cells were present within the MRH lesions and elevated serum level of TNF-α was decreased after treatment.[8] In our case 1, adalimumab acted as a steroid-sparing agent and in our Case 2, the skin lesions responded well to adalimumab.

Non-Langerhans cell histiocytosis with xanthomatous lesions and destructive arthritis is usually considered to be a variant of MRH and is often underdiagnosed. Due to the rarity of cases, the nosology of these cases as well as the association with malignancy remains to be investigated in future studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Barrow MV, Holubar K. Multicentric reticulohistiocytosis. A review of 33 patients. Medicine (Baltimore) 1969;48:287-305.  Back to cited text no. 1
Toz B, Büyükbabani N, İnanç M. Multicentric reticulohistiocytosis: Rheumatology perspective. Best Pract Res Clin Rheumatol 2016;30:250-60.  Back to cited text no. 2
Graham G, Stanfeld AG. A case of a hitherto undescribed lipoidosis simulating rheumatoid arthritis. J Pathol Bacteriol 1946;58:545-58.  Back to cited text no. 3
Krey PR, Comerford FR, Cohen AS. Multicentric reticulohistiocytosis. Fine structural analysis of the synovium and synovial fluid cells. Arthritis Rheum 1974;17:615-33.  Back to cited text no. 4
Matiz C, Ferguson PJ, Zaenglein A, Groh B, Bingham CA. Papular xanthomas and erosive arthritis in a 3 year old girl, is this a new MRH variant? Pediatr Rheumatol Online J 2009;7:15.  Back to cited text no. 5
Andrew R, Nuara A, McCollough M, Kelly E. Papular xanthomas with destructive arthritis. J Am Acad Dermatol 2013;69:e309-10.  Back to cited text no. 6
Ge JS, Hung SJ, Hsu YH, Hung JS. Rare case of multicentric reticulohistiocytosis presenting as epidermotropic papular xanthoma and double primary cancers. J Dermatol 2018;45:e138-9.  Back to cited text no. 7
Bennàssar A, Mas A, Guilabert A, Julià M, Mascaró-Galy JM, Herrero C, et al. Multicentric reticulohistiocytosis with elevated cytokine serum levels. J Dermatol 2011;38:905-10  Back to cited text no. 8


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