RESUMO
Sickle cell anemia is caused by a single mutation in the gene encoding the beta subunit of hemoglobin. Due to this mutation, sickle cell hemoglobin (HbS) polymerizes under hypoxic conditions, decreasing red blood cell deformability and leading to multiple pathological effects that cause substantial morbidity and mortality. Several pre-clinical and human studies have demonstrated that the anion nitrite has potential therapeutic benefits for patients with sickle cell disease. Nitrite is reduced to nitric oxide (NO) by deoxygenated hemoglobin contributing to vasodilation, decreasing platelet activation, decreasing cellular adhesion to activated endothelium, and decreasing red cell hemolysis; all of which could ameliorate patient morbidities. Previous work on extracellular hemoglobin has shown that solution phase HbS reduces nitrite to NO faster than normal adult hemoglobin (HbA), while polymerized HbS reduces nitrite slower than HbA. In this work, we compared the rate of nitrite reduction to NO measured by the formation of nitrosyl hemoglobin in sickle and normal red blood cells at varying hemoglobin oxygen saturations. We found the overall rate of nitrite reduction between normal and sickle red blood cells was similar and confirmed this result under partially oxygenated conditions, but normal red blood cells reduced nitrite faster than sickle red blood cells under anoxia where HbS polymerization is maximal. These results are consistent with previous work using extracellular hemoglobin where the rate of reduction by solution phase HbS makes up for the slower reduction by polymer phase HbS under partially oxygenated conditions, but the polymer phase kinetics dominates in the complete absence of oxygen.
RESUMO
BACKGROUND: Kikuchi-Fujimoto disease, which was originally described in young women, is a benign condition characterized by necrotizing lymphadenitis and fever. Even though the clinical course is usually self-limiting, it can be associated with recurrences and rarely can be associated with systemic lupus erythematosus or can be complicated with hemophagocytic lymphohistiocytosis. We report the case of a 17-year-old Sri Lankan Sinhalese schoolboy who presented with fever and cervical lymphadenopathy diagnosed as Kikuchi-Fujimoto disease and was complicated with hemophagocytic lymphohistiocytosis subsequently. Later he fulfilled the criteria for systemic lupus erythematosus. CASE PRESENTATION: A 17-year-old previously healthy Sinhalese schoolboy presented with high-grade fever associated with chills and rigors associated with loss of appetite and loss of weight for more than 40 days. On examination, he had bilateral firm matted tender cervical lymphadenopathy and firm hepatomegaly. An excision biopsy of his right cervical lymph node revealed necrotizing lymphadenitis and immunohistochemistry of a lymph node biopsy favored Kikuchi disease. Initial antinuclear antibody and anti-double-stranded deoxyribonucleic acid tests were negative and his C3 and C4 levels were normal. An infections screening was negative. He was treated with steroids. While in hospital he developed hemophagocytic lymphohistiocytosis and renal impairment. Later his antinuclear antibody titer became positive in 1:160 and fulfilled the diagnostic criteria for systemic lupus erythematosus. He was managed with steroids and immune suppressive drugs and showed remarkable improvement. CONCLUSION: Although Kikuchi-Fujimoto disease is uncommon in male patients, it needs to be considered in patients with lymphadenopathy and fever. The disease can be complicated with hemophagocytic lymphohistiocytosis and the patients need continuous monitoring for the possible development of systemic lupus erythematosus later in the course.