A 30-year-old Filipino woman with no known comorbidities and good baseline functional capacity was admitted in our institution for a one-year history of intermittent high-grade fever (Tmax 40 C), malaise, generalized weakness, anorexia, unintentional weight loss, alopecia, throat discomfort, exertional dyspnea, easy fatigability, and additive arthritis of bilateral knees, elbows, and small joints of both hands. Two months prior to admission, she consulted at a private clinic where a battery of tests showed negative Salmonella and dengue IgM and IgG, normal C-reactive protein, and normal rheumatoid factor. The patient does not smoke, drinks alcoholic beverages once a month, and denies illicit drug use. She previously worked as an adult entertainer in Japan during the early 2000s, during which she had more than 50 heterosexual partners. Her obstetric score is G2P2 (2002), with no previous fetomaternal complications. Family history is unremarkable.
On admission, she was noted to have tachycardia, fever (38.9 C), hyperemic conjunctivae, facial flushing, bilateral cervical lymphadenopathies, and arthritis of both knee joints. The initial working impression was fever of unknown origin with infection (tuberculosis and HIV), connective tissue disorder, and occult malignancy as major differential diagnoses.
Initial laboratory studies showed normocytic, normochromic anemia (hemoglobin 116 g/L), trace result on direct antiglobulin testing, and a 3.9 times elevated AST (145 U/L; reference range 15-37 U/L). Stool analysis was unremarkable, and fecal occult blood test was negative. Chest X-ray showed nonsignificant chest findings. Holoabdominal ultrasound revealed hepatomegaly with a liver span of 17.4 cm with smooth borders and a normal echo pattern but with a normal spleen. Multiple sets of sputum, stool, and urine acid-fast bacilli smears were all negative. Urinalysis showed minimal bacteriuria. ESR and CRP were both elevated. HIV antigen/antibody testing was negative. RPR, anti-HBs, anti-HCV, and HBsAg were all nonreactive. Three sets of blood cultures also turned out negative. Work-ups for infection and malignancy were unremarkable. She was initially started on piperacillin/tazobactam, omeprazole, tramadol, paracetamol, and naproxen. Naproxen was discontinued because of increase in facial flushing and periorbital edema.
On the 10th hospital day, the patient was noted to have pancytopenia (hemoglobin 108 g/L, platelet count of 139 x 109/L, WBC 3.18 x 109/L) with leukoerythroblastosis. Laboratory testing during this time revealed an increase in ESR (from 47 to 92 mm/h), increase in AST (from 145 to 553 U/L), and an increase in ALT (from 32 to 189 U/L). LDH was noted to be markedly elevated (9680 U/L; reference range 100-190 U/L). Triglycerides (3.26 mmol/L) and serum ferritin (>4500 pmol/L) were also markedly elevated. 24-hour urine collection showed total protein of 900 mg with a total volume of 1500 mL. Repeat direct and indirect antiglobulin tests were negative. Anti-cyclic citrullinated peptide was negative. Antinuclear antibody was positive but anti-double-stranded DNA was negative, and C3 was normal. Bone marrow aspiration (BMA), and biopsy was done. The BMA smear revealed a normocellular marrow with trilineage hematopoiesis and the presence of hemophagocytosis (see Figure 1). The bone marrow trephine biopsy revealed a normocellular marrow with megakaryocytic hyperplasia with moderate myelofibrosis (WHO MF Grade 2) (see Figure 2). The bone marrow acid-fast bacilli smear was negative.
Having satisfied the 2012 SLICC revised diagnostic criteria, she was then diagnosed as a case of systemic lupus erythematosus with concomitant autoimmune-associated hemophagocytic syndrome (HScore of 229 with 97.8% probability of HLH) and autoimmune myelofibrosis. She was then started on intravenous hydrocortisone (prednisone 1 mkd equivalent), hydroxychloroquine, and calcium plus vitamin D supplements. During treatment, all clinical findings (e.g., malaise, generalized weakness, throat discomfort, fever, facial flushing, lymphadenopathies, and arthritis) and laboratory data (e.g., blood counts, LDH, and liver enzymes) gradually improved. No significant treatment-related side effects were noted.
She was discharged on the 19th hospital day on oral prednisone (1 mkd), hydroxychloroquine, and calcium plus vitamin D. She was closely followed at the outpatient clinics with note of continuous improvement in symptoms and laboratory findings. Prednisone was slowly tapered down. Hydroxychloroquine and calcium plus vitamin D were continued. Good adherence to treatment plan was noted. No significant therapy-related side effects were reported by the patient. A repeat bone marrow biopsy was done four months after discharge, which revealed normocellular marrow with trilineage hematopoiesis with complete resolution of myelofibrosis and hemophagocytosis (Figure 3).