Pulmonary Alveolar Proteinosis Due to Pneumocystis carinii in Type 1 Hyper-IgM Syndrome: A Case Report

Abstract

Background: Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease. Reports of rare cases of PAP due to Pneumocystis jirovecii (P. jirovecii) exist in infants with immunodeficiency diseases, but no cases have been reported to date in pediatric patients with type 1 hyper-IgM syndrome (HIGM1). Case Presentation: Herein, we present a case of PAP secondary to P. jirovecii on an infant with HIGM1. He was admitted to our unit because of cough and tachypnea. Lung biopsy confirmed the diagnosis of PAP, whereas hexamine-silver staining of the bronchoalveolar lavage fluid identified P. jirovecii infection. No other probable cause of PAP was observed. Whole exome sequencing indicated a novel c.511dupA (p.I171N * 30) hemizygous mutation in the CD40 ligand (CD40LG) gene. He was cured with bronchoalveolar lavage and compound sulfamethoxazole tablets. Conclusions: To our knowledge, this is the first reported case of P. jirovecii infection as a reversible cause of PAP in an infant with HIGM1.

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

“…Hence, patients classically have high IgM but low serum levels of IgG and IgA, leading to an increased risk for bacterial infections. Since the CD40/CD40L pathway also mediates co-stimulation between activated CD4 + T cells and CD40-expressing monocytes, macrophages, and dendritic cells, mutations in either CD40L (X-linked) or in CD40 (AR) also lead to opportunistic infections, notably Pjp [ 257 , 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 , 310 ]. Similarly, nuclear factor-kappa-B essential modulator ( NEMO/IKKγ ) [ 311 , 312 , 313 ], inhibitor of kappa light chain gene enhancer in B cells, alpha ( IκBα ) [ 314 ], or nuclear factor kappa-B subunit 1 ( NFKB1 ) [ 315 , 316 ] are involved in CD40/CD40L signaling, and, when mutated, interfere with CD4 + T cell/APC co-stimulation, resulting in HIGM syndrome, for which there are reports of Pjp.…”

CD40LG-associated X-linked Hyper-IgM Syndrome (XHIGM) with pulmonary alveolar proteinosis: a case report

“…The present study presents a case with a novel CD40LG ( c.516T > A , p.Tyr172Ter ) truncating mutation, XHIGM, with PAP. Combined with the four previously reported patients [ 6 – 8 ], the CD40LG mutation XHIGM with PAP was characterized by the early onset of pulmonary infections at approximately the time of infancy (average: 7.75 months old). Most of these patients would experience delays in the diagnosis.…”

“…The clinical data of patients with the CD40LG mutated XHIGM with PAP are presented in Table 1 ; Fig. 2 B [ 6 – 8 ].…”

“…CD40 ligation with CD40L is important for macrophage activation. CD40LG gene mutations decrease the scavenging ability of pulmonary macrophages, resulting in the proteinosis of alveolar surfactants (for the present case, the CD40LG mutation may have led to GM-CSF dysfunction) [ 11 ]; (ii) Humoral immunodeficiency is more likely to create infective opportunities (such as Pneumocystis and fungal infections), which can weaken the phagocytic function of macrophages, and reduce the clearance of the pulmonary surfactant, eventually leading to its overabundance [ 8 , 12 ]. For the present patient, even though there was no abnormality in the screening of fungi in the alveolar lavage fluid, fungal infection could not be completely excluded, based on the predominant increase in G-test level, and the favorable response to anti-fungal therapy.…”

Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia: A case report

“…Many studies have suggested that immunodeficiency can induce PAP. However, only two cases of PAP induced by immune deficiency have been reported[ 1 - 3 ], and the remaining studies are almost all review articles. Therefore, more clinical data are needed to prove the correlation between PAP and immunodeficiency.…”