The patient, a 21-year-old Uygur male, had a history of fever and diarrhea for 8 days, with the highest body temperature of about 38.6 C, accompanied by chills, and sparse watery stool several times, without abdominal pain. Due to the intermittently increased temperature after taking non-steroidal anti-inflammatory drugs (NSAIDs), the patient was treated in the fever clinic but got a poor treatment effect, therefore he was admitted to the emergency department on October 10, 2021.
Physical examination on admission showed a body temperature of 38 C, pulse of 102 times/min, respiration of 23 times/min, and blood pressure of 125/72 mmHg, with clear consciousness, palpable spleen under the ribs. No other significant abnormalities were found in other physical examinations.
Emergency laboratory analysis in the emergency department indicated the following: white blood cell count decreased from normal range to 1.56 x 109/L (reference value, RV 3.5-9.5 x 109/L), hemoglobin was 166 g/L (RV 130-175 g/L), platelet decreased from normal range to 74 x 109/L (RV 125-350 x 109/L), aspartate aminotransferase was 150u/L (RV 15-40 u/L), lactate dehydrogenase was 1249 u/L (RV 109-245 u/L), triglyceride was 2.29 mmol/L (RV 0.45-1.7 mmol/L), sodium was 124.2 mmol/L (RV 137-147 mmol/L), fibrinogen decreased from normal range to 1.27 g/L (RV 2-4 g/L), sCD25 was 25,398 pg/mL (RV < 6,400pg/mL), ferritin was 3671u g/L (RV 30-400ng/mL), natural killer cell activity was 18.48% (RV >= 15.11%). G-test (serum (1,3)-beta-D-glucan test) was positive, GM-test (galactomannan test) was negative, and blood culture, procalcitonin, c-reactive protein, erythrocyte sedimentation rate and T-SPOT.TB test were all negative. Mycoplasma pneumoniae antibody IgM (Passive Particle Agglutination, FUJIREBIO) was 1:80 positive (RV < 1:20), Legionella pneumophila antibody IgM (ELISA, Euroimmun) was 0.82 positive (RV < 0.8). The detection of Cytomegalovirus (CMV), Epstein Barr virus (EBV), Adenovirus and Coxsackievirus were all negative (real-time PCR). The oncological and immunological indexes were normal. Plain CT scan of the thoracoabdominal basin showed mild fatty liver and splenomegaly (Figure 1). There are many small lymph nodes in the hepatogastric space and retroperitoneal space.
Referring to HLH-2004 diagnostic criteria, the patient met the following conditions: (1) Temperature > 38.5 C for more than 7 days; (2) Hemocytopenia (WBC <10 x 109/L, PLT <100 x 109/L, hemoglobin 166 g/L); (3)Splenomegaly; (4)Low fibrinogen (FIB <1.5 g/L) and high triglycerides (2.29 mmol/L), although not meeting the diagnostic criteria (3 mmol/L); (5)Ferritin > 500u g/L;(6)sCD25 > 6,400 pg/mL. Considering the definitive diagnosis of HLH, the patient was treated with 20 g immunoglobulin QD (8 days) and 0.5 g imipenem cilastatin sodium Q8H, and his leukocytes, platelets, and fibrinogen gradually returned to normal levels. However, on day 14 after his onset, the patient developed a series of symptoms of peripheral nerve involvement, as shown in Table 1.
Lumbar puncture was performed on the 16th day. Cerebrospinal fluid showed a low pressure and turbid appearance, containing 150 white cells/muL (90% lymphocytes, 10% neutrophils), protein 1.09 g/L, glucose 2.37 mmol/L, and chlorine 100.6 mmol/L; Bacteria, fungi, cryptococcus, and Mycobacterium tuberculosis were all negative; Rubella virus, CMV and EBV IgM antibody and DNA were later reported as negative. CSF and serum albumin data: CSF and serum albumin was 3.27 and 37 g/L, respectively (October 19); while 1.09 and 32.6 g/L, respectively (October 22). The albumin quotient (albumin in CSF/albumin in serum) indicated that an increased permeability of the blood-brain. No abnormality was found in CSF next-generation sequencing technology (NGS) implemented by Biotechnology Co., Ltd. Briefly, they optimized the internal index adapter and real-time analysis pipeline, established the optimal threshold for pathogen identification, and performed rapid metagenomic-NGS analysis. Peripheral neuropathy, demyelination, paraneoplastic tumor, autoimmune brain-related antibodies, serum antibodies IgM and IgG of C. jejuni were positive by enzyme-linked immunosorbent assay (ELISA), performed by Dr. Hao from the first hospital of Peking University, The values of IgM and IgG were greater than the negative control values (the cut-off values were 0.08 and 0.16 respectively) even after 1:160 dilution. Given the clinical presentation and CSF findings, based on intravenous dexamethasone of 20mg QD, the treatment regimen was adjusted to meropenem 1000 mg Q8H combined with acyclovir 60 mg Q8H and Mecobalamin 500 ug QD. On the 18th day, the patient's body temperature dropped to normal. On the 19th day, the lumbar puncture was performed again, and the cerebrospinal fluid became clear. CSF laboratory examination showed white blood cell count of 91/muL (92% single nucleus, 8% multiple nuclei), protein level of 3.27 g/L, normal glucose and chlorine, as well as negative NGS. Electromyography (Table 2) and cranial MRI were generally normal.
Considering the peripheral nerve injury and cerebrospinal fluid protein cell separation, GBS secondary to C. jejuni infection was specifically classified as Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis. On the 23rd day of onset, the diameter of the right pupil gradually recovered to 4 mm the pupillary light reflex, and the closing function of the right upper eyelid gradually recovered. On the 26th day, dexamethasone was reduced to 10 mg QD. On the 27th day, the left pupil diameter recovered to about 4 mm, and the pupillary light reflex recovered. On the 28th day, the patient defecated autonomously. On the 41st day, spontaneous urination recovered, and the patient was hospitalized for 42 days. Before discharge, the patient had left bilateral facial paralysis and mild diplopia in both eyes. One month after discharge, the patient was followed up, leaving slight facial paralysis, and other symptoms returned to normal.