When the Good Syndrome Goes Bad: A Systematic Literature Review

Abstract

BackgroundGood syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging from various infections to autoimmunity.ObjectiveThis study was to summarize patient characteristics, identify prognostic factors and define clinical subgroups of Good syndrome.MethodsA systematic literature review was conducted to include patients with Good syndrome identified in PubMed, Embase and Cochrane databases between January 2010 and November 2020. Logistic and Cox regressions were used to identify prognostic factors impacting outcomes. Clinical subgroups were defined by multiple correspondence analysis and unsupervised hierarchical clustering. A decision tree was constructed to characterize the subgroup placement of cases.ResultsOf 162 patients included in the current study, the median age at diagnosis was 58 years and 51% were male. Type AB was the most common histological subtype of thymoma, and infections as well as concurrent autoimmune disorders were identified in 92.6% and 51.2% patients, respectively. Laboratory workup showed typical findings of combined immunodeficiency. Thymoma status (odds ratio [OR] 4.157, confidence interval [CI] 1.219-14.177, p = 0.023), infections related to cellular immunity defects (OR 3.324, 95% CI 1.100-10.046, p = 0.033), infections of sinopulmonary tract (OR 14.351, 95% CI 2.525-81.576, p = 0.003), central nerve system (OR 6.403, 95% CI 1.205-34.027, p = 0.029) as well as bloodstream (OR 6.917, 95% CI 1.519-31.505, p = 0.012) were independent prognostic factors. The 10-year overall survival was 53.7%. Cluster analysis revealed three clinical subgroups with distinct characteristics and prognosis (cluster 1, infections related to cellular immunity defects; cluster 2, infections related to other immunity defects; cluster 3, infections related to humoral and phagocytic immunity defects). A decision tree using infection types (related to humoral and cellular immunity defects) could place patients into corresponding clusters with an overall correct prediction of 72.2%.ConclusionsInfection type and site were the main prognostic factors impacting survival of patients with Good syndrome. We identified three subgroups within Good syndrome associated with distinct clinical features, which may facilitate the study of underlying pathogenesis as well as development of targeted therapy.

A Case of Severe COVID-19 in a Patient with Good's Syndrome

“…Only 6-10% of patients with thymoma develop GS and no specific histopathological subtype has been associated with the syndrome [2] . As in the case we report, hypogammaglobulinaemia does not always improve after thymectomy, indicating thymoma management alone is not sufficient to resolve this disorder [1] . Other therapeutic strategies are mainly supportive with antimicrobials and Ig replacement, recommended in GS patients who present with recurrent infections [2] .…”

“…GS is a rare adult-onset combined immunodeficiency characterized by thymoma and hypogammaglobulinaemia [1] . Most cases occur between the ages of 40 and 70, with equal distribution between the sexes [2] .…”

“…Other therapeutic strategies are mainly supportive with antimicrobials and Ig replacement, recommended in GS patients who present with recurrent infections [2] . Infection remains the leading cause of mortality in patients with GS [1,2] and prognosis is believed to be worse compared with other adult immunodeficiencies [1,[3][4][5] . Moreover, compared with other primary humoral deficiencies, bronchiectasis caused by thymoma-associated hypogammaglobulinaemia has a higher mortality rate [5] .…”

“…Humoral immunodeficiency (peripheral B-cell decrease in particular) has been correlated with a predisposition to severe infections [2] . Improved recognition of this rare disorder, more frequent use of Ig replacement, expanded availability of various antimicrobial agents, and better supportive care in the recent decade, seem to be the main reasons for the downward trend in mortality [1] . Due to its rarity and the absence of clear clinical and laboratory criteria, the diagnosis, as happened in this case, is often late, which may lead to a worse prognosis.…”

Good’s Syndrome: Time to Move on From Reviewing the Past

“…It then became apparent that this syndrome included reduced or absent mature B cells ( 3 ). In the latest review of GS, four cohort studies reported a total of 44% of individuals who had complete absence of peripheral B cells, while 50% had low levels ( 4 ). Thus, it is appropriate that reduced or absent B cells be accepted as an additional diagnostic criterion for GS ( 5 , 6 ).…”