A 20-year-old woman was presented to the emergency clinic with fever and sore throat for one week and joint pain, weakness in limbs, and slight numbness of fingertips and tongue. She denied any tobacco or alcohol (illicit drugs) use, and her family history was not notable. After admission, she continued to experience a high fever (Tmax 40 C). One week after her admission, scattered congestive pinpoint itching rashes appeared on her chest, abdomen, back, and limbs, without ulceration or scaling, accompanied by liver function abnormalities (alanine aminotransferase, ALTmax 227 IU/L, reference range of 7-40 IU/L; aspartate transaminase, ASTmax 193 IU/L, reference range of 13-35 IU/L). The rash was noticeable when the body temperature rose and faded when the body temperature dropped. Inflammatory markers such as serum ferritin (max to >7,500 ng/ml, reference range 11-306.8 ng/ml), erythrocyte sedimentation rate (ESR, max to 50 mm/h, reference range 0-20 mm/h), C-reactive protein (CRP, max to 104 mg/L, normal <5 mg/L), and lactate dehydrogenase (LDH, max to 900 IU/L, reference range 100-240 IU/L) were all significantly elevated. The lymph node ultrasound revealed extensive enlarged superficial lymph nodes (Figure 1).
The clinical diagnosis of AOSD is generally reached by exclusion while investigating a patient with a fever of unknown origin. We carried out detailed screenings for infectious diseases, autoimmune diseases, and tumors. Laboratory examinations for common pathogens (respiratory pathogens, such as influenza virus, mycoplasma, chlamydia, legionella, adenovirus, etc.) and specific disease-related pathogens (cytomegalovirus/Epstein-Barr virus, mycobacterium tuberculosis, rickettsia of typhus, Coxiella burnetii of Q fever, Salmonella typhi, Brucella, etc.) were all negative. The blood culture was repeatedly negative, and screening tests for AIDS, hepatitis B, hepatitis C, and syphilis were negative. Antibodies that indicate some autoimmune diseases, such as the anti-double-stranded DNA antibody, antineutrophil cytoplasmic antibodies (ANCA), anti-extractable nuclear antigen (ENA) antibodies, immunoglobulins, protein electrophoresis, immunofixation electrophoresis, complements, rheumatoid factor were all no meaningful found. No significant findings were found in tumor markers, bone marrow biopsy, and imaging examinations of underlying malignant tumors. According to the Yamaguchi criteria, the patient was diagnosed with AOSD.
Methylprednisolone (60 mg Q.D.) was administrated as starting dose with subsequent tapering. After glucocorticoid treatment, her main symptoms were relieved, and inflammatory markers rapidly decreased, but the paresthesia and decreased sensation in her extremities decreased muscle strength with MRC (Medical Research Council) grades 2-3, tendon reflexes diminished to the disappearance, and imbalance progressed remarkably so that she was not able to walk or write; even words started slurring in the third week. We ordered an MRI of the spine with no positive findings, excluding the possibility of the patient's lumbosacral ganglion compression. Heavy metal and toxicants blood tests were negative. Head MRI and cerebrospinal fluid (CSF) examination were normal. The anti-ganglioside GQ1b antibody was negative in both serum and cerebrospinal fluid. Polymyositis antibodies, and paraneoplastic syndrome-related antibodies (Hu, Yo, and Ri antibodies) showed no meaningful findings. We performed the electrophysiological examination, and nerve and muscle biopsy revealed immune-mediated extensive peripheral nerve injury (Supplementary Figures 1-3). Intriguingly, electron microscopy images of nerve biopsy demonstrate the typical manifestation of distal axonal degeneration due to nerve injury:Wallerian degeneration (Figure 2). Paresthesia, muscle weakness, and tendon reflexes were fully recovered with MRC grades five after 9 months of glucocorticoid therapy in the patient, and slight numbness of the fingers and toes remained. She got fully recovered after more than 3 years of regular follow-up.