Unusual organ involvement in sarcoidosis: sarcoid myopathy and peritoneal sarcoidosis

Abstract

Myopathy and peritoneal involvement are rare complications of sarcoidosis, and the latter can mimic malignancy with peritoneal dissemination. In this case, a patient with a history of polyarthritis and positive rheumatoid factor presented with proximal muscle weakness and abdominal pain. Biopsies of muscle and peritoneum revealed non-caseating granuloma suggesting sarcoidosis. Ocular and pulmonary involvement later developed and confirmed the diagnosis of sarcoidosis.

Background

While extrapulmonary involvement is present in half of patients with sarcoidosis, sarcoid myopathy is often asymptomatic, and peritoneal sarcoidosis is rare.^{1 2} Polyarthritis with low titre rheumatoid factor positivity can develop prior to other features of sarcoidosis.^{3 4} The diagnosis of sarcoidosis can be challenging in patients when extrapulmonary presentations precede its typical lung findings.

Case presentation

A 64-year-old woman presented to our hospital with pedal and periorbital oedema, malaise and proximal muscle weakness. Three months prior, periorbital swelling followed by oedema in bilateral lower extremities had developed. Two months prior to this presentation, the patient had difficulty arising from chairs due to muscle weakness in her arms and legs. She also reported a weight gain of 6 kg in 3 months, abdominal pain, nausea and non-bloody loose stools. There were no fever, chills, night sweats, cough, sputum, shortness of breath, morning stiffness, joint pain, vomiting, haematochezia, dysuria or haematuria. Seven years earlier, rheumatoid arthritis was suspected due to polyarthritis, elevated C reactive protein (CRP) and a positive rheumatoid factor. Her joint symptoms were well controlled with methotrexate, bucillamine and tacrolimus, but methotrexate and tacrolimus were discontinued due to abnormal liver function tests 2 years prior to presentation. She had hypertension but did not take any medications nor supplements. The patient was a professional cleaner and lived alone. She smoked one pack of cigarettes per day for 40 years and drank 0.5–1 L of beer daily. She did not use illicit drugs, had no recent travel or exposure to animals.

On physical examination, temperature was 36.9°C, blood pressure was 157/82 mm Hg, pulse 112 per minute, respiratory rate 18 per minute and oxygen saturation on ambient air was 97%. The patient was alert. Periorbital oedema was present. There was no jugular venous distension or cervical lymphadenopathy. The heart and lung examinations were unremarkable. Abdomen was non-tender without organomegaly or a palpable mass. There was oedema of lower legs which was more prominent on the right. Strength was 5 out of 5 in all muscle groups, except for the right biceps, triceps, anterior tibial muscle and gastrocnemius muscles being 4 out of 5.

Investigations

Laboratory studies showed a serum sodium of 139 mmol/L, a potassium of 2.8 mmol/L, a chloride of 97 mmol/L, a blood urea nitrogen level of 13 mg/dL and a serum creatinine (Cr) of 0.61 mg/dL. Liver function tests were normal. Lactate dehydrogenase was 266 U/L. Creatine kinase was 81 U/L and aldolase was 15.3 U/L (normal: 2.7–7.5). Total protein was 6.5 g/dL and albumin was 3.1 g/dL. The complete blood counts showed a white blood cell count of 11,6×10⁹ (/L), with 82.6% neutrophils. Haemoglobin was 15.5 g/dL, haematocrit was 44.9% and mean corpuscular volume (MCV) was 87 fL. Platelet count was 275 000 /µL. Urinalysis showed haematuria and mild proteinuria (0.45 g/gCr). C3 and C4 were 67 mg/dL and 20 mg/dL. Immunoglobulin panel was negative for monoclonal pattern. CRP was 1.88 mg/dL. Chest X-ray and EKG were unremarkable. CT with contrast from the neck to the pelvis material showed a misty mesentery with moderate ascites, accompanied by uterine myoma and thickening of the wall of the right colon without hilar adenopathy or lung parenchymal lesions (figure 1). MRI of the right arm revealed diffuse high short T1 inversion recovery (STIR) signals at the biceps, triceps, deltoid, supraspinatus, spinal erector and intercostal muscles. Exploratory laparoscopy showed multiple white nodules in the round ligament of the liver, greater omentum and peritoneum (figure 2).

Figure 1.

CT scan of abdomen with contrast material showed misty mesentery (arrows) and ascites (arrowheads).

Figure 2.

Exploratory laparoscopy showed multiple white nodules in the round ligament of the liver and peritoneum.

Differential diagnosis

The differential diagnosis of muscle weakness and peritoneal nodules included paraneoplastic muscle weakness or inflammatory myositis arising from peritoneal carcinomatosis of unknown origin, tuberculosis and alcoholic myopathy, sarcoidosis and fungal infections such as histoplasmosis.

Rheumatoid factor was 35 IU/mL and anticyclic citrullinated peptide antibody, antinuclear antibodies, anti-Ro/SSA, myositis-specific antibodies including antiaminoacyl tRNA synthetase antibody were negative. CA125 and CA19-9 were 270.1 U/mL (reference range 0–35 U/mL) and <0.6 U/mL. Uterine mass was consistent with myoma.

Muscle-biopsy of the right triceps showed non-caseating granulomas, without myonecrosis or degeneration (figure 3A). Pathology of the peritoneal biopsy also showed non-caseating granuloma with multinucleated giant cells in the serosal surface, suggestive of sarcoidosis. (figure 3B) Angiotensin-converting enzyme was 44.3 U/L (reference range 8.3–21.4 U/mL), lysozyme was 25.5 µg/mL (reference range 5.0–10.2 µg/mL) and soluble interleukin-2 receptor was 4247 U/mL (reference range 157–474 U/mL). Interferon gamma release assay was negative, as were acid fast bacilli (AFB) culture of the peritoneal specimen and the ascites, which was exudative and lymphocyte-predominant with negative cytology.

Figure 3.

(A) Muscle biopsy. (B) Peritoneal biopsy. Pathology of biopsy showed non-caseating granuloma with multinucleated giant cells.

Treatment

Oral prednisolone 20 mg daily and methotrexate failed to improve her musculoskeletal pain, and the patient complained of blurry vision. Ophthalmic examination showed choroidal nodules and snowball-like vitreous opacities, consistent with intraocular sarcoidosis. Infliximab was added.

Outcome and follow-up

Six cycles of infliximab improved her symptoms, which was subsequently discontinued. Two weeks later, the patient developed cough and fever. CT scan showed hilar and mediastinal lymphadenopathy and bilateral ground-glass opacities. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) scan also showed hypermetabolic bilateral hilar and mediastinal lymphadenopathy, which was consistent with lung sarcoidosis. Bronchoalveolar lavage (BAL) revealed lymphocytosis (82%) and no neutrophils. Transbronchial biopsy demonstrated non-caseating granulomas. AFB culture of BAL, PCR for pneumocystis jirovecii and antigens of cryptococcus neoformans and aspergillus were all negative. Diagnosis of sarcoidosis was confirmed, based on radiographic presentation, pathological evidence of non-caseating granulomas and exclusion of other diseases.⁵ Infliximab with prednisolone 40 mg (1 mg/kg) was reinstituted, and the patient remained well after tapering off prednisolone 3 months later.

Discussion

A 64-year-old woman with history of arthritis who presented with proximal muscle weakness and abdominal pain was diagnosed with sarcoidosis complicated by muscle, peritoneal, eye and lung involvement. Sarcoidosis is an inflammatory disorder of unknown cause that is characterised by granuloma formation. Any organ may be involved, including lung, skin, eyes, kidneys, liver, spleen, bones, joints and the cardiovascular and nervous systems. Half of patients with sarcoidosis have extrapulmonary involvement, but only 5%–9% of patients have extrapulmonary sarcoidosis without observable pulmonary involvement.⁶ The diagnosis of sarcoidosis in this case was initially challenging due to absence of lung findings but typical sarcoid features of myopathy and peritoneal pathology. While sarcoid myopathy is often asymptomatic, symptomatic patients have three clinical patterns: nodular, acute myositis and chronic myopathy, with varying degrees of myalgia and weakness.¹ Muscle biopsy helped unmask granulomatous myositis in this case. Peritoneal sarcoidosis is uncommon, and the combination of exudative ascites, elevated CA-125 and peritoneal nodules could easily be misdiagnosed as cancer, tuberculosis or fungal infection.²

The majority of patients with sarcoidosis are women, and the patients may present with abdominal pain, ascites and increased abdominal girth.⁷ Five cases of elevated CA-125 level have been reported in patients with peritoneal sarcoidosis. All cases were female and CA-125 had normalised after treatment with steroids in three cases.⁸ Histology of different organs including typical lung involvement confirmed the diagnosis of sarcoidosis in this case. In retrospect, polyarthritis and positive rheumatoid factor suggest that the patient may also have had sarcoid arthropathy. In patients with sarcoidosis, arthralgia often precedes the diagnosis and resolves within 6 weeks.³ Low titres of rheumatoid factor have been reported in sarcoidosis.⁴

In summary, a 64-year-old woman with a history of polyarthritis presented with proximal muscle weakness and abdominal pain with elevated aldolase and ascites. Muscle and peritoneal biopsy provided diagnostic clues for sarcoidosis with myopathy and peritoneal involvement, when hilar adenopathy was absent on chest X-ray and CT scan.

Learning points.

• Sarcoid arthritis or arthralgia may be subtle and often precedes systemic manifestations of sarcoidosis.

• Sarcoid myopathy is often asymptomatic but symptomatic myopathy requires a biopsy to confirm non-caseating granuloma.

• Peritoneal sarcoidosis is rare and can mimic peritoneal dissemination of malignancy.

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