We report the case of a previously healthy African 39-year-old female patient, with a recent history of cesarean section without complications, being discharged after three days of hospitalization. It was her first pregnancy, being submitted to cesarean section due to failure to progress in labor. The newborn was apparently healthy. Approximately fourteen days later, she was admitted to the Emergency Department with diffuse abdominal pain and fever (38o Celsius). Endocervical ultrasound showed the presence of uterine fluid which was drained and sent for microbiologic analysis. Empirical antibiotic therapy was started with cefazolin and the patient was admitted to the Obstetrics and Gynecology Department with the diagnosis of endometritis. Cultural tests isolated Prevotella timonensis and antibiotic therapy was switched to ceftriaxone plus clindamycin and gentamicin, with a decrease of acute phase biomarkers. However, the patient continued to present sustained high fever (38-39,5o Celsius) with new-onset painful cervical and axillary lymphadenopathies and a generalized, non-pruritic maculopapular rash (Figure 1), without the involvement of palmar and plantar surfaces of hands and feet. She was transferred to the Internal Medicine Ward for further investigation
She progressed with acute dyspnea and increased work of breathing with impending respiratory failure - the respiratory rate of 30 breaths per minute and pO2 of 51 mmHg. Chest x-ray showed diffused bilateral opacities and CT-pulmonary angiography excluded the presence of pulmonary thromboembolism, revealing bilateral pleural effusion, ground-glass opacities dispersed by all pulmonary parenchyma and pericardial effusion (Figure 2).
Acute pulmonary edema was assumed, and she showed partial improvement of the respiratory failure on endovenous loop diuretics. Concomitantly, she presented two episodes of tonic-clonic seizures. Head-CT- scan revealed unspecific alterations of density and cranial magnetic resonance imaging (MRI) confirmed the presence of water's diffusion restriction at cortical areas and revealed the presence of a left temporal hyperdense area at the T2 sequence that could be related to an inflammatory process (Figure 3). A lumbar puncture was performed with no pathological findings after cerebrospinal fluid (CSF) cytological, biochemical and microbiologic examination. Anticonvulsant therapy was started with levetiracetam 1.5g every 12hours with subsequent suppression of abnormal neural activity.
Laboratory findings revealed autoimmune hemolytic anemia, leucopenia, elevated erythrocyte sedimentation rate, hyperferritinemia, hypertriglyceridemia, proteinuria and hypoalbuminemia. The auto-immune panel revealed: positive ANAs (antinuclear antibodies) with a 1:640 titer, hypocomplementemia, and positive anti-dsDNA. Anti-SSA and anti-SSB, anti-PL7, anti-RNP, anti-U1-SnRNP, anti-Pm-Scl75 were also positive. Blood cultures were systematically negative, and IgG for EBV (Epstein-Baar virus) and CMV (Cytomegalovirus) was positive, but IgM was negative. Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Herpes Simplex Virus (HSV), Human Papillomavirus (HPV) and Human Herpesvirus (HHV)-6,7,8 screening was also negative. Testing for Plasmodium, Toxoplasma, Treponema pallidum, Rickettsia spp and Mycobacterium tuberculosis and spp was negative as well. Laboratory findings and respective evolution are shown in Table 1. Full-body CT-scan revealed hepatomegaly and innumerous cervical and axillary lymph nodes. Cervical node biopsy showed follicular hyperplasia and subcapsular areas with necrosis, compatible with Kikuchi-Fujimoto Disease versus SLE. Medullar bone biopsy showed an increase in megakaryocytic lineage, sins of phagocytic activity, high levels of IL-2 and CD25-CXCL9 positivity. Systemic IL-2 was elevated too (Table 1). Given the proteinuria, the patient was eligible for a kidney biopsy, which could not be performed due to clinical instability.
Considering an inaugural flare SLE with multisystemic involvement (Systemic Lupus Erythematosus Disease Activity Index of 38 points) and concomitant secondary HLH (Hscore of 216 points), pulses of methylprednisolone were started (1g/day for three days). Anakinra (200mg twice/daily) and Cyclophosphamide according to the Eurolupus protocol were also started. By the end of the first cycle of Cyclophosphamide, she presented a new episode of acute pulmonary edema, delirium, fever recurrence, abdominal pain recrudescence, profuse diarrhea without blood or mucus, the new elevation of acute phase biomarkers and hemolytic anemia worsening (Table 1). Blood cultures, coprocultures, and clostridium screening were all negative as well as cytomegalovirus viral load. Broad-spectrum antibiotherapy with ceftazidime/avibactam was started and, despite negative CMV viral load, ganciclovir was also initiated as well as antifungal therapy with fluconazole. Despite broad antimicrobial therapy and blood transfusion support the patient maintained clinical worsening, evolving with shock and requiring transitory vasopressor, thereby the second cycle of cyclophosphamide was postponed, and she was admitted to the Intensive Care Unit (ICU). Abdominal CT revealed small and large intestine dilatation, vascular engorgement and mesenteric densification which were compatible with inflammatory/ infectious enteropathy. Endoscopic studies ruled out gastrointestinal hemorrhage and biopsies only showed mucosal edema; serum immunoglobulins were normal. ASCA and anti-LKM antibodies were also negative (Table 1). Due to anorexia and severe weight loss, parenteral nutrition was initiated. After three days of supportive care in the ICU, the patient had no recurrence of fever or seizure activity. She also presented respiratory failure improvement and hemolytic anemia resolution. However, she continued to present profuse watery diarrhea with severe hypoproteinemia and hypoalbuminemia.
After the exclusion of an infectious process, a Lupus PLE was assumed, and Cyclophosphamide protocol was resumed. As we resumed the induction protocol, the patient evolved with sustained clinical improvement. Parenteral nutrition was suspended, and oral feeding was tolerated. She was discharged by the end of the fourth cycle of Cyclophosphamide, maintaining follow-up as an outpatient.