We report the case of a 14-year-old Caucasian boy with persistent diarrhea admitted in February 2015 to Department of Pediatrics, County Hospital in Oradea, Romania, for investigations. No significant personal, familial history or physical features were observed at the time. The laboratory report showed only mild dehydration, with no inflammation and immunological deficits, the bacteriological stool exam detected no pathogen agent and abdominal ultrasonography revealed no abnormalities. In the differential, inflammatory bowel disease, celiac disease and infectious enterocolitis were ruled out and he received symptomatic treatment. Five months later, in July 2015, the patient returned to Hospital reporting weight loss (7 kg over the last month) and chest burns. Complete blood count (CBC) revealed bicytopenia: anemia and neutrophilia. Further investigations consisted of a positive HIV enzyme-linked immunosorbent assay (ELISA) test therefore he was transferred to Department of Pediatrics, Infectious Disease Hospital, Cluj-Napoca, Romania. There was no significant family history for HIV infection and from the patient's personal medical history it is worth mentioning a surgical intervention at one year of age and several minor dental interventions.
On physical examination, he presented cachexia and white lingual deposits.
Initially, HIV ELISA test was reactive and HIV infection was confirmed through Western blot test; viral load was very high (Table 1), CD4 and CD8 T-lymphocytes levels were low. CBC revealed severe neutropenia (neutrophil cells count was 0), leukopenia, lymphopenia, and normochromic normocytic anemia. Esophagitis secondary to C. albicans infection was found at superior endoscopy and taught to be the cause for the chest burns. Other associated opportunistic infections were ruled out.
Neutropenia was interpreted as secondary to HIV injury on the bone marrow and ART was initiated consisting of Darunavir, Ritonavir, Raltegravir and Lamivudine, for a period associated with Enfuvirtide. Prophylactic antibiotic treatment of opportunistic infections and antifungal treatment of candida was associated. As a response to treatment, HIV viral load decreased from 1 872 739 copies/mL to 88 copies/mL in eight weeks of ART, but neutropenia persisted. Due to severe neutropenia, the patient received granulocyte-colony stimulating factor (G-CSF). CD4 T-lymphocytes number and neutrophil count remained low (Figure 1), with G-CSF having a prompt but brief favorable response, continuous administration of at least two doses per week being necessary.
Persistence of neutropenia in parallel with favorable evolution of viremia, raised the suspicion of another responsible cause. In the differential, etiologies like infections (hepatitis B and C, EBV, CMV, parvovirus B19, tuberculosis, toxoplasmosis, and Mycobacterium avium - normal serological tests and chest X-ray) and lymphoma (normal cervical, thoracic, and abdominal computed tomography) were ruled out. A bone marrow aspirate revealed granulocytic hypoplasia, pleomorphic lymphoid population, reactive macrophages (irregular nuclear shape, increased in volume, intranuclear vacuoles, eosinophilic cytoplasm), which presented hemophagocytosis and lymphocytosis (Figures 2 and 3) and, in association with fever, bicytopenia (neutrophilia and moderate normochromic normocytic anemia), hypofibrinogenemia and hypertriglyceridemia allowed the diagnosis of HLH secondary to HIV infection.
Cortisone (Dexamethasone) therapy and intravenous immunoglobulins were added to the treatment, but there was no improvement therefore HLH-2004 protocol was initiated. It was followed for a prolonged period due to the persistence of cytopenia. CD4 T-lymphocytes levels and the neutrophil count showed significant increase simultaneously only after a period of six months from the beginning of HLH-2004 protocol.
The patient evolution was good but suddenly, during hospitalization he presented severe back pain, which initially responded to intravenous pain killers but soon after he required bed immobilization to control the pain. Magnetic resonance imaging described a thoracic (T11) vertebral fracture line, vertebral compressions, and osteopenia. A rheumatology consult led to the finding of a low level of serum vitamin D, folic acid, and calcium. The diagnosis of osteomalacia due to calcium and vitamin D deficiency secondary to prolonged cortisone therapy was established.