Rheumatology Advance Access originally published online on April 29, 2008
Rheumatology 2008 47(7):1102-1103; doi:10.1093/rheumatology/ken131
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Multicentric reticulohistiocytosis: a lesson in screening for malignancy
Department of Rheumatology, Musgrave Park Hospital, Belfast, UK
Correspondence to: A. Millar, Department of Rheumatology, Musgrave Park Hospital, 20 Stockman's Lane, Belfast, BT9 7JB, UK. E-mail: auleenmillar{at}hotmail.com
SIR, We present the case of a 65-yr-old female smoker with a 2-month history of peripheral arthralgia, referred to a tertiary rheumatology service as a possible case of RA. Her symptoms were consistent with an inflammatory polyarthropathy, with symmetrical pain and stiffness of both hands, wrists, elbows, shoulders and knees. Clinical examination confirmed the presence of synovitis of the affected joints including the DIP joints. Skin nodules were noted on the extensor surfaces of several fingers (Fig. 1), the nail folds and the face. They measured 
0.3 x 0.5 mm2 and were firm and mildly tender to touch.
|
The patient had been weakly RF-positive for several years prior to development of joint symptoms. Initial investigations revealed an RF of 55 IU/ml (normal range 0–25), a CRP of 40 mg/l, an ESR of 31 mm/h with a normal haemoglobin and biochemistry screen. ANAs, extractable nuclear antigens, ANCAs, complement, creatinine kinase levels and urinalysis were normal. The initial work-up included chest X-ray, ultrasound of abdomen and a transthoracic echocardiogram, which were all reported as normal.
A punch biopsy of a skin lesion identified an intradermal nodule composed predominantly of multinucleate giant cells with abundant eosinophilic cytoplasm mixed with histiocytes. The giant cells were weakly Periodic acid-Schiff positive, strongly CD68 positive and S-100 negative. The pathological findings in this clinical setting confirmed the diagnosis of multicentric reticulohistiocytosis (MRH).
Patients with aggressive RA frequently suffer from fatigue, weight loss and raised inflammatory markers in the setting of uncontrolled disease. Management typically involves immunosuppressive therapy. MRH, however, is associated with underlying malignancy in 25% of the cases. Our patient proceeded to a CT scan of chest, abdomen and pelvis. This demonstrated mediastinal adenopathy in the pre-tracheal, carinal and right hilar groups. No focal lung or interstitial lung process was visualized and the remainder of the examination was normal. Bronchoscopy was performed but no endobronchial lesion was identified, and washings taken for cytology and culture (routine and specifically for TB) were negative. A pre-tracheal node biopsy, however, confirmed the underlying diagnosis of metastatic large cell carcinoma.
MRH is a rare histiocytic proliferative disease and an important differential diagnosis of rheumatoid and other inflammatory arthropathies. Fewer than 200 cases have been reported in the world-wide literature. Once diagnosed, patients with MRH warrant thorough investigation to exclude underlying malignancy that may not be apparent on routine assessment.
MRH joint disease is characteristically a destructive and deforming symmetrical polyarthritis with a predilection for the DIP joints. The arthropathy usually precedes nodular skin involvement, which follows after an average of 3 yrs [1]. In a minority of cases, the skin lesions may precede joint disease (18%) or both may develop simultaneously (21%). More than 50% of the cases have mucosal involvement affecting the mouth, gingiva, pharynx, larynx and sclera [2]. In the absence of skin lesions, the diagnosis can be challenging.
Clinically, the DIP involvement is a useful feature in the differentiation of MRH joint disease from RA. MRH has previously been associated with a negative RF and only marginally raised ESR; however, our patient was weakly RF-positive for some years prior to presentation. A recent report documented a case of MRH that was positive for antibodies against cyclic citrullinated peptide [3].
Patients with MRH may develop constitutional symptoms of pyrexia and weight loss. Nodules have been found in the bone marrow, skeletal muscle, lymph nodes, heart and other vital organs [4]. Whilst the nodules themselves are benign, the discovery of systemic lesions will usually require tissue diagnosis to exclude underlying neoplastic disease.
Although no single site or type of malignancy has been associated with MRH, the condition has been described in association with a wide variety of malignancies including melanoma, sarcoma, leukaemia, lymphoma and carcinomas of the breast, colon, bronchus, cervix, stomach and ovaries. Symptoms of MRH will usually precede those of the neoplasm and can relapse with the recurrence of the malignancy. There has been a single report of the development of MRH in a patient with a past history of breast cancer and no evidence of either recurrent or new malignancy [5].
This case highlights an important but rare cause of a symmetrical polyarthropathy. It emphasizes the need for thorough investigation beyond routine screening tests to exclude associated malignancy and the importance of tissue diagnosis of both skin and systemic lesions.
Disclosure statement: The authors have declared no conflicts of interest.
 |
References |
|---|
 Top References |
|---|
- Barrow MV, Holubar K. Multicentric reticulohistiocytosis. A review of 33 patients. Medicine (1969) 48:287–305.[Medline]
- Katz RW, Anderson KF. Multicentric reticulohistiocytosis. Oral Surg Oral Med Oral Pathol (1988) 65:721–5.[CrossRef][Web of Science][Medline]
- Chauhan A, Mikulik Z, Hackshaw KV. Multicentric reticulohistiocytosis with positive anticyclic citrullinated antibodies. J Natl Med Assoc (2007) 99:678–80.[Medline]
- Yee KC, Bowker CM, Tam CY, et al. Cardiac and systemic complications in multicentric reticulohistiocytosis. Clin Exp Dermatol (1993) 18:558–68.
- Santilli S, Monaco A, Cavazzini P, Trotta F. Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the distal interphalangeal finger joints. Ann Rheum Dis (2002) 61:485–7.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||