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Cutaneous nodules in a patient with polyarthritis

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A 43-year-old normo-uricaemic man with bilateral, symmetrical, destructive polyarthritis involving the distal and proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, shoulders, knees and ankles, developed multiple, non-itchy nodules on the hands, arms and the trunk (shown in the figure).

Figure Multiple nodules on the patient's arms

Questions

1
What is the diagnosis ?
2
What conditions come in the differential diagnosis ?
3
What conditions are associated with this entity ?
4
How is this condition managed ?

Answers

QUESTION 1

Multicentric reticulohistiocytosis (MCRH). This is a rare systemic disease characterised by tissue infiltration with lipid-laden histiocytes (macrophages) and multinucleated giant cells. Destructive polyarthritis and skin lesions are the most common findings.

QUESTION 2

MCRH should be differentiated from rheumatoid arthritis with nodulosis, xanthomata, tophaceous gout, sarcoidosis, psoriatic arthritis, methotrexate-induced nodulosis, and fibroblastic rheumatism (boxes FB1 and FB2).

Figure FB1
Figure FB2
Figure FB3

QUESTION 3

MCRH has been associated with a variety of conditions such as hypercholesterolaemia, malignancy, tuberculosis, diabetes mellitus, hypothyroidism, Sjogren's syndrome, primary biliary cirrhosis, myopathy, and pregnancy.

QUESTION 4

Corticosteroids, antimalarials, and cytotoxic agents have been tried with variable results. No therapy has been consistently effective, but early and aggressive treatment with cyclophosphamide, chlorambucil or methotrexate may help prevent the devastating arthropathy and disfiguring skin lesions. In some cases removal of the associated malignancy may result in the resolution of arthritis and skin lesions.1

Discussion

MCRH is a multisystem disorder primarily affecting the joints and skin, although any organ system can be involved. It occurs in midlife (mean age at onset 43 years) and women are twice as often affected as men. It is seen mostly in whites, although cases have been reported in all races. Arthritis is frequently the presenting manifestation and occurs as the sole presenting feature in 45% of patients; 30% of patients exhibit cutaneous lesions in addition to arthritis at presentation.2 The arthritis is erosive and has a propensity to involve the distal interphalangeal joints, in addition to other joints. This feature helps in differentiation from rheumatoid arthritis (table). Skin involvement consists of reddish brown nodules which vary in size from 1 to 10 mm and which can coalesce to form plaques. Ulceration is not common. The cutaneous involvement may be disfiguring, although spontaneous regression is known. Cardiac, pulmonary pleural, gastrointestinal and lymphoreticular involvement is also known to occur.

Table Radiological differentiation between rheumatoid arthritis (RA) and MCRH

Histopathology reveals tissue infiltration by lipid-laden histiocytes and multinucleated giant cells. The stimulus that triggers the inflammatory response is not known.3 Cytokines such as interleukin-1 beta and platelet- derived growth factor may play a role.4 The primary cell involved in the reactive inflammatory response is the phagocytic tissue histiocyte (macrophage). While uncontrolled proliferation of these reticulohistiocytes is seen in several infectious and malignant conditions, there is no direct evidence of a particular organism or neoplasm involved in the aetiopathogenesis of MRCH.3 There is evidence of tuberculosis exposure in a third of cases with active tuberculosis present in 5%.3 Malignancies are reported concurrently with MCRH in 15–28% cases.3 These include breast, colon, bronchus, cervix, stomach, and ovary (usually adenocarcinoma), as well as cases of melanoma, sarcoma, leukaemia and lymphoma.5About half of the patients with MCRH have hypercholesterolaemia.2

MCRH must be differentiated from several disorders presenting with cutaneous nodules and polyarthritis (boxes FB1 and FB2). Differentiation from rheumatoid arthritis is often possible on clinicoradiologic grounds (table) without the need for a biopsy.6Vasculitides, erythema nodosum and rheumatic fever can also be easily differentiated on clinical grounds. The arthropathy of fibroblastic rheumatism, unlike MCRH, does not usually progress rapidly.7

In view of the relative rarity of the condition, no definite treatment guidelines for MCRH exist. Success has been reported with oral daily cyclophosphamide (1.25–2.2 mg/kg body weight), chlorambucil (0.1 mg/kg), and methotrexate (7.5–10 mg/week).8 9 The optimum duration of treatment is not known.

Final diagnosis

Multicentric reticulohistiocytosis.

References

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