Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication of initiation of highly active antiretroviral therapy in HIV-infected patients. As the immune system recovers, an inappropriate inflammatory response often occurs that causes significant disease. It is most commonly seen in patients naïve to therapy with CD4+ T-lymphocyte counts <100 cells/cmm and usually presents as a flare of mycobacterial, cytomegalovirus, or herpes zoster infections. Less commonly, this syndrome occurs in response to noninfectious triggers and results in autoimmune or malignant disease. Here we present the first case of acute poststreptococcal glomerulonephritis associated with varicella zoster virus and IRIS in an adolescent with perinatally acquired HIV and hepatitis C virus infections. Our patient was not naïve to therapy but was starting a new regimen of therapy because of virologic failure and had a relatively high CD4+ T-lymphocyte count. This case report indicates that IRIS remains a concern after initiation of a new highly active antiretroviral therapy regimen in HIV-infected patients with high viral loads, even in the presence of CD4+ T-lymphocyte counts >100 cells/cmm. It may present as infectious, malignant, or autoimmune conditions including poststreptococcal glomerulonephritis.
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September 2012
Case Report|
September 01 2012
Acute Poststreptococcal Glomerulonephritis: A Manifestation of Immune Reconstitution Inflammatory Syndrome
Julie Martin, MD;
aThe Saul Krugman Division of Pediatric Infectious Diseases, and
Address correspondence to Julie Martin, MD, Pediatric Infectious Disease, NYU Medical Center, 550 First Ave, New York, NY 10016. E-mail: julie.martin@nyumc.org
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Aditya Kaul, MD;
Aditya Kaul, MD
aThe Saul Krugman Division of Pediatric Infectious Diseases, and
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Robert Schacht, MD
Robert Schacht, MD
bDivision of Pediatric Nephrology, Department of Pediatrics, New York University School of Medicine/Bellevue Hospital, New York, New York
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Address correspondence to Julie Martin, MD, Pediatric Infectious Disease, NYU Medical Center, 550 First Ave, New York, NY 10016. E-mail: julie.martin@nyumc.org
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Pediatrics (2012) 130 (3): e710–e713.
Article history
Accepted:
March 14 2012
Citation
Julie Martin, Aditya Kaul, Robert Schacht; Acute Poststreptococcal Glomerulonephritis: A Manifestation of Immune Reconstitution Inflammatory Syndrome. Pediatrics September 2012; 130 (3): e710–e713. 10.1542/peds.2011-1246
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Non-classical Acute Poststreptococcal Glomerulonephritis associated with non-classical Immune Reconstitution Inflammatory: The strength of the evidence.
Regina Celia de Souza Campos Fernandes, MD, MSc, DSc, a, b and Enrique Medina-Acosta, MSc, PhD c
a Faculty of Medicine of Campos, b Municipal Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodeficiency Syndrome, and c Molecular Identification and Diagnosis Unit, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.
Address correspondence to Regina Celia de Souza Campos Fernandes, MD, Rua Conselheiro Otaviano 241, Campos dos Goytacazes, RJ, CEP 28010-140, Brazil. E-mail: reg.fernandes@bol.com.br
Financial disclosure: The authors have indicated they have no financial relationships relevant to this article to disclose.
Funding: No external funding.
Top the Editor:
Dr. Martin and colleagues recently reported the first case indicative of Acute Poststreptococcal Glomerulonephritis (APSGN) associated with Immune Reconstitution Inflammatory Syndrome (IRIS) in an adolescent with perinatally acquired HIV and Hepatitis C virus infections, and who was successfully treated with highly active antiretroviral therapy (HAART).1 Atypical features of both APSGN and IRIS hallmarked their case definition. In view of the potential novelty of this case, we would like to point to important limitations of their study. With relation to APSGN, the concomitant absence of hypertension and edema did not ascertain classic nephritic syndrome associated to APSGN. In APSGN complicated by renal failure, one expects very low values of C3; in contrast, in this patient, they were close to cut-off values (62.5mg/75mg). Furthermore, the observed expressive decay in hemoglobin level from 13.4 to 7g/dL is incompatible with classic APSGN,2 even considering the incipient renal failure (serum creatinine was 2.4; normal values for age group ranged 0.6-1.4 mg/dL). In this scenario, it is important to rule out hematological toxicity associated with Zidovudine used by the patient, which would be defined by macrocytosis (Mean Corpuscular volume (MCV) >100 fL). To explain the anemia, Dr. Martin and colleagues made differential diagnosis with hemolytic uremic syndrome (HUS), which classically includes hemolytic anemia, renal failure and thrombocytopenia. However, no supporting laboratory test results were provided for thrombocytopenia and elevated lactic dehydrogenase (a marker of cell injury). It is important to point that the infection with HIV per se is a cause of diarrhea-negative HUS,3 and that the simultaneous occurrence of diarrhea-negative HUS and APSGN has been described in children.4 Dr. Martin and colleagues attributed the persistence of ASO high titers to immune dysregulation with inability to clear antigen. However, in the context of the well-succeeded HAART and in the absence of streptococcal antibiotic resistance such explanations are not plausible. That finding is best interpreted as part of a normal response to HIV infection, with polyclonal B cell activation and hypergammaglobulinemia or new exposure to streptococcal antigens. The persistence of microscopic hematuria for 2 years in this patient was tentatively assigned to either an infection with a more virulent streptococcal strain or an immunologic dysregulation secondary to HIV infection. However, this presentation is perfectly admissible given the prior renal disease HIV-associated, as demonstrated by renal biopsy, and a more advanced age of this patient.5
A distinctive characteristic of IRIS is a severe immunosuppression.6 The marked atypical feature of this case was, in contrast, an elevated basal CD4 count and its decrease after HAART. Furthermore, the relative ratios of CD4 cells were not provided, which are required to define the state of immunosuppression (<15% in severe immunosuppression).
In view of the lack of characterization of a severe immunosuppression, and the explanations here offered for the clinical evolution of APSGN, we conclude that the association IRIS-APSGN claimed by Dr. Martin and colleagues must be revisited.
References 1. Martin J, Kaul A, Schacht R. Acute poststreptococcal glomerulonephritis: a manifestation of immune reconstitution inflammatory syndrome. Pediatrics. 2012;130(3):e710-713 2. Kliegman R, Nelson WE. Nelson textbook of pediatrics. 18th ed. Philadelphia: Saunders; 2007. 3. Kelleher P, Severn A, Tomson C, et al. The haemolytic uraemic syndrome in patients with AIDS. Genitourin Med. 1996;72(3):172-175 4. Laube G, Sarkissian A, Hailemariam S, et al. Simultaneous occurrence of the haemolytic uraemic syndrome and acute post-infectious glomerulonephritis. Eur J Pediatr. 2001;160(3):173-176 5. Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol. 2008;19(10):1855-1864 6. French MA. Immune Reconstitution Inflammatory Syndrome: A Reappraisal. Clin Infect Dis. 2008
Conflict of Interest:
None declared