Acute sarcoidosis: a difficult diagnosis

L. S. Teh, G. M. Coombes, R. H. MacDonald1, R. J. Prescott2, D. M. Dietch and A. K. P. Jones

Rheumatology and
1 Pathology, Hope Hospital, Salford Royal Hospitals NHS Trust, Stott Lane, Salford M6 8HD and
2 Department of Pathology, Blackburn Royal Infirmary, Bolton Road, Blackburn BB2 3LR, UK

SIR, We report a case that illustrates the difficulties in the diagnosis of pyrexia of unknown origin [1]. A young male caucasian presented with fever, rash, polyarthralgia and lymphadenopathy. An initial diagnosis of acute toxoplasmosis proved incorrect, as did the subsequently revised one of adult Still's disease. The correct diagnosis proved to be acute sarcoidosis made 6 months after presentation, when a Kveim test proved positive 4 months after the intradermal injection.

A 30-yr-old white police officer was admitted as an emergency case with a 1-week history of sore throat, sweating attacks, intermittent skin rash and flitting polyarthralgia. His wife and daughter were well and the family's pet cat was also healthy. There was no recent history of travel abroad or relevant past medical history. On examination, he had a temperature of 39.4 et al.C with a blanching maculo-papular erythematous rash over the hands, arms and thighs. There was mild synovitis of the proximal interphalangeal (PIP)/metacarpophalangeal joints of both hands, the right knee, both ankles and the third PIP joint of the left foot. The only abnormal initial routine investigations were a raised white cell count of 13.1 x 109/l (80.5% granulocytes, 11.9% lymphocytes, 7.6% monocytes and <1% eosinophils) and an erythrocyte sedimentation rate (ESR) of 50 mm/1st h. Chest and hand radiographs, Monospot test, immunoglobulins, cryoglobulins and complement levels were normal. He responded to naproxen and was presumed to have a viral illness.

Ten days after discharge, he was readmitted with increasing lethargy, night sweats, asymmetrical joint synovitis and the intermittent rash. He was pyrexial at 39 et al. C with small, palpable cervical, axillary and inguinal lymph nodes. The white cell count and ESR remained elevated. Abdominal ultrasound and a white cell scan were normal. CT scan of the thorax and abdomen showed axillary and mild pretracheal lymphadenopathy. Toxoplasma IgG antibody titres were raised at 1/16 000, with low IgM titres. The rest of the infection screen and autoantibody screen were negative. T-cell subsets showed a normal CD4/CD8 ratio and HIV test was negative. Angiotensin converting enzyme (ACE) levels were normal. His joint pain and swelling responded to diclofenac sodium, but the fever, rash and lymphadenopathy persisted. The ESR remained raised, the haemoglobin fell and he developed hypoalbuminaemia. The significance of the raised IgG anti-Toxoplasma antibody was unclear and a serum polymerase chain reaction test for Toxoplasma was arranged. This was negative, but because of his deteriorating clinical condition he was treated with anti-Toxoplasma therapy (pyrimethamine and sulphadiazine). The pyrexia remained unaltered on this treatment, which was stopped after 5 days because of severe nausea.

Further investigations, including bone marrow aspirate, lymph node biopsy and liver biopsy, were unhelpful. He continued to have night sweats, intermittent skin rash, polyarthralgia and weight loss. The possibility of adult Still's disease was entertained and he was started on aspirin. The pyrexia settled but the raised ESR, anaemia and hypoalbuminaemia persisted and a Kveim test was performed. Six weeks later, a punch biopsy was performed at the site of inoculation. Histology was negative for sarcoidosis. He continued with night sweats and lethargy even when the aspirin dose was increased to 1200 mg q.i.d. and subsequently changed to indomethacin. Four months after the Kveim test he developed a nodule at the site of intradermal inoculation and a repeat biopsy showed non-caseating granulomatous infiltrate compatible with sarcoidosis (Fig. 1Go). His symptoms responded dramatically to prednisolone 30 mg/day and within 1 month the ESR, haemoglobin and albumin were normal for the first time in 8 months (Fig. 2Go). He regained his premorbid weight. The prednisolone was slowly reduced and stopped after 12 months. He has remained well without prednisolone for the past 24 months.



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FIG. 1. Kveim biopsy showing non-caseating granulomatous infiltrate consistent with sarcoidosis.

 


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FIG. 2. Fluctuation of the ESR (solid line) and haemoglobin (dotted line) during the course of disease.

 
This case illustrates the difficulty of diagnosing pyrexia of unknown origin. Acute sarcoid arthritis is a recognized presenting feature of sarcoidosis but less than 10% of cases present with extrapulmonary manifestations alone [2], and the arthritis usually occurs in association with bilateral hilar lymphadenopathy and erythema nodosum [3]. The normal chest radiograph and non-specific skin rash led to difficulty in diagnosing this patient's condition. Although normal ACE levels can occur in patients with sarcoidosis [4], this can be misleading. What was more surprising was the delayed reaction to Kveim extract at 4 months. The Kveim granuloma usually develops in 75% of patients with sarcoidosis 2–6 weeks after inoculation [5]. In extrathoracic sarcoidosis, as in our patient, overall positive reponse rates vary from 26 to 50% and the positivity decreases with increasing chronicity irrespective of disease activity (to 62% in disease of less than 2 yr duration and 38% in disease of more than 2 yr duration) [6]. The positive Kveim test in our patient at 4 months thus strongly supports the diagnosis of sarcoidosis.

There were also many similarities between this case and acquired toxoplasmosis [7]: evanascent macular rash, fever, weight loss, arthralgia and upper cervical lymphadenopathy. The presence of very high IgG titres to Toxoplasma gondii and the fact that the patient had a pet cat prompted the initial diagnosis of toxoplasmosis. However, there was no response to pyrimethamine and sulphadiazine, subsequent serial IgM anti-toxoplasmosis antibodies remained low and both the polymerase chain reaction and lymph node biopsy failed to substantiate the diagnosis.

Our patient also fulfilled the criteria for adult Still's disease [8] and was treated with aspirin and then indomethacin. His response was suboptimal, but 20–25% of patients with adult Still's disease do not respond to non-steroidal anti-inflammatory drugs [810]. Steroids are the main form of treatment in this group of resistant patients. Perhaps our patient should have been given steroids earlier, but this may have masked a more serious diagnosis such as underlying lymphoma, other malignancy or rare immunodeficiency. It would have invalidated the Kveim test [6] and the true diagnosis would never have been elucidated.

In summary, sarcoidosis can mimic acquired toxoplasmosis and adult Still's disease. It should be considered in the differential diagnosis of a patient presenting with pyrexia of unknown origin, flitting polyarthralgia, evanescent rash and lymphadenopathy. The response to the Kveim test may be delayed beyond 6 weeks and early ‘blanket’ treatment with steroids can mask the true diagnosis.

Notes

Correspondence to: Dr L. S. Teh, Department of Rheumatology, Ward 13, Level 5, Blackburn Royal Infirmary, Bolton Road, Blackburn BB2 3LR, UK. Back

References

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Accepted 10 January 2000





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