Sjögren's Syndrome With Nervous System Injury Combined With Pulmonary and Osseous Cryptococcosis

A Case Report

Liping Xu; Xinwei Song; Yan Zhang; Na Lin; Ji-An Wang

Disclosures

J Med Case Reports. 2021;15(325) 

In This Article

Case Presentation

A 46-year-old otherwise healthy Chinese female officer with a history of repeated limb numbness about 21 months was admitted to the Department of Rheumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, China on 4 November 2016. Without a history of tobacco and alcohol consumption, she suffered numbness of her right foot since February 2015 that soon spread to her limbs. Her electromyography examined in local hospital indicated peripheral nerve damage, her blood test showed antinuclear antibodies (ANA) 1:320 and anti-Sjögren's syndrome-A (anti-SSA) antibodies positive, and her salivary gland Emission Computed Tomography (ECT) demonstrated low function, in addition, her labial gland biopsy revealed the number of infiltrating lymphocytes was more than 50 in 4 mm2 under the high-power field of vision. Thus, she was diagnosed with Sjögren's syndrome and treated with methylprednisolone (MP) of 40 mg each day, hydroxychloroquine (HCQ) of 200 mg twice a day to suppress excessive immune inflammation, and immunoglobulin of 0.4g/kg/day for 5 days to modulate the immunity. Despite temporary relief, her limb numbness aggravated in March 2015. Then, she gained a prescription of mycophenolate mofetil (MMF) 1.0 g/day plus the same treatment as before, and her symptoms alleviated again. But she was hospitalized with a 1-month history of aggravated limb numbness, shortness of breath, and weakness in November 2016. There was no history of other illnesses. On examination, she had no fever (temperature 36.7 °C), blood pressure (BP) 118/78 mmHg, heart rate (HR) 68 beats per minute, with decreased pulmonary sounds in the lower lobe of the left lung, and a few wet rales, as well as declined muscle strength about grade 4, with superficial sensory and positional hypoesthesia. The rest of her physical examination was negative.

According to the respiratory manifestation, a lung computed tomography (CT) scan was conducted, and the result showed multiple nodules in the lower lobe of the left lung and middle lobe of the right lung (Figure 5a), which was considered an infection; hence, we conducted possible pathogen tests, which revealed that serum cryptococcal capsular polysaccharide antigen was positive. Her sputum tests for bacteria, acid-fast bacilli, fungi, and serum G test (serum fungi-specific antigen detection), GM test (serum Aspergillus-specific antigen detection), T-SPOT (T-SPOT.TB test), human immunodeficiency virus (HIV), and rapid plasma reagin (RPR) test were negative. As for the evaluation of SS, serological tests showed that ANA was strongly positive at about 1:640, and anti-SSA and anti-centromere antibodies were positive, but the remaining immunologic tests were negative, including anti-neutrophilic cytoplasmic autoantibodies (ANCA), anti-glomerular basement membrane antibodies, anti-dsDNA, anti-Sm, and multiple tumor markers. Meanwhile, C-reactive protein and erythrocyte sedimentation rate (ESR) were normal. In addition, electromyography indicated serious damage in the limb-peripheral nerve, especially in lower limbs. Cranial magnetic resonance imaging (MRI) revealed multiple demyelinating lesions in the white matter of both cerebral hemispheres (Figure 1). CT scan displayed multiple high-density lesions in the lumbar vertebrae. MRI demonstrated an abnormally low signal in the corresponding vertebral bodies at T1 and T2 sequences (Figure 2). Positron emission tomography–computed tomography (PET/CT) (Figure 3) showed multiple lesions with high 18F-fluorodeoxyglucose (18F-FDG) uptake in lung and vertebral bodies, and the radiologist believed that abnormal lesions were most likely to be cancer. Finally, her lung and bone tissue biopsies revealed granulomatous lesions with visible Cryptosporidium and positive ink staining (Figure 4) and negative acid-fast staining, which was consistent with Cryptococcus infection, and no Cryptococcus neoformans were found in the cerebrospinal fluid (CSF).

Figure 1.

Cranial MRI revealing multiple demyelinating lesions in the white matter of both cerebral hemispheres

Figure 2.

a CT scan showing multiple high-density lesions in lumbar vertebrae. b, c MRI demonstrating abnormal low signal in the corresponding vertebral bodies at T1 and T2 sequences. Red arrows point to the lesions

Figure 3.

PET/CT showing multiple lesions with high 18F-FDG uptake in lung (a) and vertebral bodies (b)

Figure 4.

a Lung tissue biopsy showing granulomatous lesions [hematoxylin and eosin (HE), ×100]. b Lung tissue biopsy showing granulomatous lesions; green arrow points to Cryptosporidium [periodic acid–Schiff (PAS), ×400]. c Positive ink staining

She was eventually diagnosed with neurologic complications related to Sjögren's syndrome combined with pulmonary and osseous cryptococcosis. The dose of prednisone was reduced to 10 mg/day, MMF was discontinued, and fluconazole (400 mg/day) was given for 6 months. Meanwhile, to modulate the immunity, immunoglobulin of 0.4 g/kg/day was injected intravenously for 5 days. Her CT scan showed that the lung lesions had reduced within 3 weeks (Figure 5b), and 3 months later, these lesions had disappeared. However, during this period, the symptoms of limb numbness worsened, indicating that SS was active. Although the infection was not fully controlled, she received therapy with prednisone (30 mg/day) since the 45th day after the treatment of fluconazole. Fortunately, her neurological symptoms and the infection were both controlled during the recent 1-year follow-up period.

Figure 5.

a CT scan showing multiple nodules in the left lung. b CT scan showing a reduction in lung lesions. Red arrows point to the lesions

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