Multicentric reticulohistiocytosis presenting with papulonodular skin eruption and polyarthritis

ARTICLE

Auteur(s) :, Shahram Baghestani^1,*, Farrokh Khosravi², Mohsen Dehghani Zahedani³, Abdol-Ali Mahboobi¹

¹Hormozgan University of Medical Sciences, Bandar Abbas Medical School, Department of Dermatology, PO Box 79145-3654, Bandar Abbas, IranFax: (+98) 761 2248123.
²Department of Internal Medicine, Rheumatology division
³Department of Pathology

accepté le 2 Juin 2004

Case report

She had married 11 years previously and had a 4-year-old son. Her family history and personal history were unremarkable.

Physical examination revealed multiple discrete, smooth surface red-brown papules and nodules measuring 0.3 to 2 cm in diameter over the ears, nasolabial fold, upper lip, nose, knuckles, elbows, wrists, nail folds and a few lesions over her trunk ( (figures 1A and 1B) ). The oral mucous membrane was free of lesion. She had bilateral and symmetrical arthritis of the hand, foot, knee, elbow and ankle joints.

A 6mm punch skin biopsy from a lesion over the dorsum of her hand was stained with hematoxylin-eosin ( (figures 2A and 2B) ) which revealed an infiltrate composed of numerous mononuclear and multinucleated histiocytes with “ground glass” periodic acid-schiff reactive eosinophilic cytoplasm admixed with lymphocytes. The multinucleated histiocytes were oval and polygonal with irregular distribution of nuclei characteristic of multicentric reticulohistiocytosis (MRH).

Previous treatment with diclofenac and prednisolone was not effective. She refused any medication and did not come for follow-up visits for 2 years due to personal reasons.

After 2 years of untreated disease the patient was reevaluated. Some of her skin lesions over the elbows had became larger, softer and also sessile and some of the lesions over her forearm and abdomen had disappeared leaving atrophic scars ( (figure 1C) ). New papular skin eruptions with the previous characteristics had appeared over her neck ( (figure 1D) ) and abdomen. Histopathology of the abdominal skin biopsy was similar to the previous biopsy. Arthritis had increased significantly in all the involved joints although no evidence of major organ involvement was detected.

Plain X-ray showed massive destruction in the articular surface and significant loss of joint space in involved joints, which had been normal at initial presentation. Erosive arthritis had started at the margins of the joints and had progressed to punched out lesions on the articular surface and to severe joint destruction. Periarticular osteoporosis and early joint space loss were absent in this case. Significant erosions of the proximal and distal interphalangeal joints were observed ( (figure 3A) ).

MRI showed early focal chondrolysis and subchondral bone erosion, joint effusion and synovial proliferation in the knees ( (figures 3B and 3C) ), hands and wrist joints.

Work up for malignancy including abdominal sonography, chest X-ray, chest and abdominal CAT scans were negative. Liver and kidney function tests, lipid profile, anti nuclear antibody, anti-double strand DNA antibodies, rheumatic factor, complement 3 & 4 and C-reactive protein were within normal limits but the erythrocyte sedimentation was 30 mm/1^st h. Tuberculin skin test was negative.

To our knowledge, the natural course of untreated multicentric reticulohistiocytosis has not been described previously.

Discussion

Skin lesions consist of multiple firm reddish-brown papulonodular lesions, decreasing in number in a cephalo-caudal direction. Cutaneous lesions predominantly affect extensor surfaces of the hands, forearms, face, scalp, ears, and rarely lower trunk and legs. Proximal nail fold involvement gives a characteristic coral bead appearance. Skin lesions have a tendency to wax and wane leaving a permanent scar until the disease spontaneously resolves [5].

Involvement of oral mucosa, gingiva, pharynx and the sclera is present in more than 50% of the patients. Characteristically, the lips and tongue are involved. Xanthelasma is seen in 30% of the patients [6].

Erosive arthritis begins at the margins of the joints, progressing to osseous defects and severe joint destruction. In contrast to rheumatoid arthritis, periarticular osteoporosis and early joint space loss are absent in MRH. In addition, significant erosions of distal interphalangeal joints seen in MRH are not common in rheumatoid arthritis [7]. The interphalangeal joints are the predominant sites of involvement in the hands, but eventually all of the synovium lined joints become affected, with arthritis mutilans the end result in one third of the cases. Since arthritis often precedes cutaneous manifestations, careful roentgenologic evaluation may play a key role in early diagnosis [8].

While mucocutaneous eruption and polyarthritis characterize the disease, multiple organ involvement including the heart, skeletal muscle, pleura and gastrointestinal tract have been involved in reported cases [9, 10].

MRH has been associated with a number of autoimmune diseases with systemic complications and 15-28% of the reported cases have had concomitant malignancy (table 1( Table 1 )).

There is evidence of tuberculosis exposure in one third of the cases with active tuberculosis being present in 5% [11].

Definite diagnosis of MRH is made by skin or synovial biopsy. Characteristic histological features are the presence of numerous multinucleated giant cells and oncocytic histiocytes showing an abundant eosinophilic, finely granular cytoplasm, often with a ground glass appearance [12]. The presence of prominent markers of monocyte/macrophage origin, as well as tumor necrosis factor alpha, interleukin-1beta and interleukin-6 has been reported [13].

MRH can be a relatively stable and self-limiting disease but still causes permanent joint destruction and deformities with arthritis mutilans in a substantial percentage of cases.

The therapeutic trend in MRH is to treat the patient early and aggressively in order to prevent the devastating arthropathy and disfiguring cutaneous sequelae. Corticosteroids, antimalarials, various antimitotic compounds such as penicillamine and topical nitrogen mustard have been used in the treatment of MRH. Administration of immunosuppressive drugs is accompanied with variable results although cyclophosphamide is reported to have a higher success rate than other agents which have been tried [14].

Combination of systemic steroids with azathioprine [15, 16], low dose methotrexate [17] alone or in combination with chloroquine [18], anti-tumor necrosis factor [19] and alendronate [20] have been used with success. Cyclosporine A has been reported to be effective after an unsuccessful attempt of treatment with cyclophosphamide and corticosteroids were tried in a patient with systemic lupus erythematosus complicated with MRH [21]. Regression following resection of an associated malignancy has been reported [22, 23].

In this case, typical papulonodular skin eruption, symmetric erosive arthritis and characteristic histopathologic findings in two separate skin biopsies confirmed the diagnosis of MRH. Skin lesions have been reported to appear at an average of 3 years after arthritis [24], in contrast to our case in whom the lesions appeared a few months before the arthritis.

After 2 years of natural course of disease, multiple new dome shaped papules ranging from 1-5 mm appeared over her neck and around the ears in addition to large soft and sessile nodules on her elbows and forearms ( (figures 1C and 1D) ) and except for a few papules around the upper lip, no mucosal involvement was seen.

No evidence of the other organ involvement or active tuberculosis was seen and after two years of further investigation, no associated autoimmune diseases or neoplasm was detected in this untreated case.

Similar to previously reported cases, erosive arthritis started at the margins of the joints in our patient, progressing to punched out lesions on the articular surface which led to severe generalized joint destruction including the distal interphalangeal joints. Periarticular osteoporosis and early joint space loss were absent in this case ( (figure 3A) ).

Yamada et al. reported destructive changes of the right knee with well circumscribed marginal erosions, plus bulky masses, with an intermediated intensity on T1-weighted images, in the joint space extending to the suprapatellar bursa representing a marked proliferation of synovial tissue in the joint space [25]. This finding was similar in our patient who had a lesser extent of synovial proliferation ( (figures 3B and 3C) ).

MRH has a tendency to resolve spontaneously in an average of 8 years but the prognosis of this disease is not good as the disease is disabling and malignant diseases occur in 15 to 25% of the cases [26].

Destructive and mutilating articular changes in this untreated case again confirmed the fact that early and aggressive treatment is warranted.
Table 1 Diseases associated with multicentric reticulohistiocytosis

References

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