Adolescent with Henoch–Schönlein purpura glomerulonephritis and intracranial hemorrhage possibly secondary to the reactivation of latent CMV

Abstract

We treated a 14-year-old boy with Henoch -Schönlein purpura nephritis (HSPN) who died of an intracranial hemorrhage (ICH). Although ICH is a rare complication of HSPN, the consequence of this complication is sometimes very serious. 1 But there are no reports on the pathology and pathogenesis of ICH occurring in the course of HSPN. We examined the autopsied brain tissue and renal biopsy specimen using in situ hybridization (ISH) and polymerase chain reaction (PCR) of human cytomegalovirus (HCMV). The results indicated that he had had latent HCMV infection on admission to hospital. This suggests that reactivation of latent HCMV infection superimposed on HSPN worsened his vasculitis and resulted in fatal ICH. This is the fi rst report investigating the brain pathology of ICH as a result of severe vasculitis of HSPN. Case reportFive years prior to coming to Surugadai Nihon University Hospital , a 9-year-old boy was admitted to a local hospital for abdominal pain and vomiting. He was diagnosed as having HSPN because purpura had appeared on his legs. He was followed as an outpatient by the hospital and was admitted fi ve times after his fi rst admission due to abdominal colic. The patient had proteinuria and hematuria and was given only dipyridamole during these periods. Two months prior to admission to Surugadai Nihon University Hospital he had pretibial edema, hypertension and abdominal distention with heavy proteinuria. He was referred to Surugadai Nihon University Hospital because of his severe nephritis.On admission he was 6 kg heavier than 1 month previously, and he had hypertension (140/92 mmHg) and anasarca. The laboratory fi ndings on admission were as follows: blood urea nitrogen 25.6 mg/dL, creatinine (Cr) 2.29 mg/dL, total protein (TP) 4.1 g/dL, albumin (Alb) 2.3 g/dL, total cholesterol (T-cho) 272 mg/dL, urine red blood cells >100 per high-power fi eld, and urinary protein 819 mg/dL (3.62 g/day), and creatinine clearance (Ccr) 39.6 mL/min, IgG 338 mg/dL, IgA 233 mg/dL, third component of complement (C3) 97.7 mg/dL, fourth component of complement (C4) 19.2 mg/dL, anti-nucleic antibody, anti ds-DNA antibody, proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) and myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) were negative.Based on these fi ndings a clinical diagnosis of nephronephritic HSPN was made, and treatment with oral prednisolone (2 mg/kg) was started. A renal biopsy showed diffuse mesangial proliferative glomerulonephritis, which was compatible with the International Study of Kidney Disease in Children (ISKDC) grade Vb. Intravenous methylprednisolone pulse therapy in combination with urokinase (3 days/week) was administered for 3 weeks. 2 After this therapy his serum creatinine decreased to 1.5 mg/dL. We then conducted double fi ltration plasmapheresis for 3 days to remove the IgA immune complex (IgA-IC), 3,4 which reduced IgA-IC from 3 mg/dL to 1 mg/dL. But on day 26 he had a fever and complained of a severe headache and delirium. Brain computed tomography (CT) showed a smal...

Cytomegalovirus infection in childhood-onset systemic lupus erythematosus

“…However, development of a comorbid CMV infection in an individual with any autoimmune disease can lead to adverse outcomes. For example, CMV infection has been associated with worsening of the vasculitis in a patient with Henoch Schonlein Purpura, resulting in a fatal intracranial hemorrhage, and has also been associated with triggering the potentially serious complication of macrophage activation syndrome in other autoimmune diseases [3,55]. …”

Herpesvirus Infection in Development of Hemorrhagic Vasculitis in Children (Literature Review)

“…HV is a fairly common disease in childhood, which is difficult; it often takes a recurrent course with the involvement of kidneys in pathological process, with violation of their function and formation of chronic glomerulonephritis with outcome in chronic renal failure [3,[9][10][11]. The study of various aspects of the course of HV will help to reach a new therapeutic level of this disease.…”

“…Their occurrence in children can contribute to frequent acute infectious diseases, foci of chronic infection, drug allergy, hereditary predisposition to vascular or rheumatic diseases. Bacterial or persistent viral infections, allergies or burdened allergic anamnesis are two factors that form the background for hypersensitivity of an organism or act as a trigger, provoking factors [6,7,9,10,[13][14][15][16]. Changes in HV in the damaged area of the vessel are diversefrom ischemia to hemorrhage, necrosis, and infarction.…”

“…That is, in patients with vasculitis syndrome, active replication of CMV (68%) and HHV-6 (64%) was more frequent, compared to the active replication of Epstein-Barr, which is noted almost half as often (36%) [33]. X. Murakami, S. Takahashi, Y. Kawakubo, N. Kinukawa, S. Funaki, K. Harada in 2008 described the case of a teenager with SHP and intracranial hemorrhage, possibly, as the authors note, associated with persistence of herpesvirus infection -CMV [10].…”

Central Nervous System Involvement in Henoch-Schonlein Purpura in Children and Adolescents

“…Many of them are written in the past century, when MRI with new sequences was not readily available. Moreover histologic confirmation of CNS involvement in HSP occurred casuistically [21, 22]. That is why the pathogenic mechanisms of CNS involvement in reported cases remain unclear.…”