Latin American consensus on the supportive management of patients with severe combined immunodeficiency

Abstract

Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 ''agreed'' and 38 ''nonagreed'' statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID. (J Allergy Clin Immunol 2019;144:897-905.)

Combined immunodeficiencies

“…However, patients with IEI, depending on the type and severity of the immunological compromising, may experience an absent or reduced response to vaccination. 8 Additionally, some patients with IEI may be susceptible to the occurrence of infectious complications when submitted to vaccines containing live attenuated agents, as already mentioned in BCG vaccination ( Table 4 ). 37 Therefore, decisions about indicating or contraindicating vaccines to a patient with IEI must take into account the immunological condition determined by the underlying disease, which may be aggravated by complications or the use of medications.…”

“…It is not clinically apparent at birth and infectious complications usually appear during the first year of life, being potentially fatal until the age of two, if immune reconstitution is not performed. 7 , 8 …”

“…However, in Latin America and in many parts of the world where neonatal screening for SCID is not yet routinely available, the diagnosis is made most of the time with infections and severe complications and referral for definitive treatment at a specialized center is delayed. 8 …”

Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease

“…Following a diagnosis of SCID-X1, therapeutic measures must be applied as soon as possible, including transfer to a specialized center, establishment of immunoglobulin replacement therapy (IgRT) and appropriate antimicrobial prophylaxis (15,(27)(28)(29)(30). HSCT or gene therapy should be performed as soon as possible to restore immunity, for instance adhering to the consensus guidelines proposed by the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies (EBMT/ESID) (31) or USIDnet advice.…”

A novel homozygous RAG1 mutation is associated with severe combined immunodeficiency and neurological presentations

“…4 The primary clinical manifestations frequently present between 4 and 7 months of age including chronic diarrhea, insufficient growth, and recurrent infections. 5 The neurodevelopmental defects are not common and progressive in SCID patients, nevertheless, seizure and microcephaly have been observed in some cases. 6 Moreover, infants who suffer from SCID are more vulnerable to be infected with community-acquired infections that lead to end-organ dysfunction.…”