Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.

     

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenstr?m's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.     

Évolution d’une thrombopénie chronique idiopathique en cours de grossesse (62 grossesses)

Purpose

The aim of this study was to assess the platelet count outcome during a pregnancy occurring in a series of 62 women followed for a chronic idiopathic thrombocytopenia.

Methods

We studied the medical files of women who had a previous history of chronic idiopathic thrombocytopenia persistently below 150 G/L for at least 1 year, and who became pregnant over a 14-year period.

Results

Sixty-two pregnancies (including 41 in women suffering from an immune thrombocytopenic purpura according to updated definition criteria) which occurred in 50 women, were analysed. At the beginning of the pregnancy, platelet count was above 150 G/L in 16% of the cases and lower than 50 G/L in 8%. Platelets decreased by more than 25% for 55% of the pregnancies, remained stable during pregnancy in 33% and improved in 12%. Platelet count remained above 50 G/L in 70% of the pregnancies and higher than 100 G/L in 27%. Mean nadir was 84 G/L at 31 weeks of gestation. A treatment was started in 40% of pregnancies, among them 64% of the cases during the last month only in order to allow locoregional anaesthesia at delivery. Platelet count was below 150 G/L at delivery in 82% of the women (116 ± 56 G/L). No bleeding occurred in 83% of the pregnancies. Neonatal mean platelet count was 225 ± 87 G/L, thrombocytopenia occurred in 17% of the babies (platelet count below 150 G/L), without any serious bleeding.

Conclusion

Pregnancy worsens chronic idiopathic thrombocytopenia outcome in half of the cases, most of the time without any haemorrhagic complications.