Background and Aims

IL-12 receptor deficiency is a well-characterized primary immunodeficiency that leads to infections mainly with mycobacteria and Salmonella. The aim of the study is to report manifestations and causes of vasculitis complicating IL-12 receptor deficiency.

Methods

This is a retrospective study including patients with IL-12 receptor deficiency who developed vasculitis during a follow up of 10 years.

Results

Among 14 children affected by IL-12 receptor deficiency, three have developed vasculitis. They were two boys and one girl. Vasculitis was diagnosed at the age of 8 months, 22 years and 3 years, respectively. Edema and purpuric eruptions were present on the lower extremities in three patients. One patient had acute ischemia by thrombosis of the left humeral artery. Skin biopsy showed leukocytoclastic vasculitis. Serologic tests for vasculitis (rheumatoid factor, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative in all cases. Infectious tests revealed Salmonella Enteritidis in blood and stool cultures of two patients. In these two cases, the successful treatment of septicemia using antibiotics was accompanied by the disappearance of Vasculitis. Vasculitis relapsed in one patient in the same territory, concomitant with a recurrent Salmonella sepsis. Limb amputation was performed in another patient after the failure of the discharge with aponeurotomy.

Conclusions

Clinicians should be aware of possible infectious causes of vasculitis in IL-12 receptor deficiency patients. Patients should be first tested for specific Salmonella infection. In addition, autoimmunity was also reported as a possible cause of vasculitis in these patients.

Background and Aims

Leukocyte adhesion deficiency (LAD) is a defect of cellular adhesion molecules with deficiency of various glycoproteins including LFA-1 resulting in a combined immunodeficiency disorder with recurrent bacterial and fungal infections. The aim of our study is to describe LAD’s clinical features.

Methods

From 1998 through 2018, 18 patients (from 12 families and 11 consanguineous marriage) were enrolled. Each of them had a severe (<1%: n=15) or moderate (1-30%: n=3) decreased expression of LFA-1 and benefited from chemoprophylaxis with Cotrimoxazole and Itraconazole. Clinical data was retrospectively analyzed.

Results

Sex ratio was 0,8. Mean age was 29 days [2;180] at first symptoms and 7,6 years [0,16;31] at diagnosis. First signs included delayed separation of the umbilical cord (n=13), omphalitis (n=12), oral thrush (n=11) and sepsis (n=10). The most common infections were recurrent skin infections (n=16), ENT infections (n=7), pneumonia (n=7), urinary tract infections (n=5) and gastrointestinal infections (n=5). The main infectious agents were enterobacteriaceae (n=10), staphylococcus (n=9), pseudomonas aeruginosa (n=9), candida (n=5) and corynebacterium (n=4). All patients had marked neutrophilic leukocytosis with mean neutrophilis count at 46323 cells/mm³. Four patients were lost to follow-up. Issue was fatal in 7 cases (mean age at death= 6,5 years). Five patients had allogeneic hematopoietic stem cell transplant (HSCT), 2 of whom were cured.

Conclusions

LAD is usually fatal before 2 years of age. Moderate cases can live longer with appropriate antimicrobial therapy. Those patients with successful HSCT can have a better quality of life.

Background and Aims

Disseminated BCG disease is often fatal and results from impaired immunity. The aim of our study is to describe the outcome of BCG disease in immune-compromised (PIDs) children receiving haematopoietic stem cell transplantation (HSCT).

Methods

We included all patients how underwent HSCT for PIDs in whom BCG infection occurred before or after HSCT. Isoniazide and rifampycine were discontinued before conditioning to ovoid drug interactions and switched to ethambutol and ciprofloxacin.

Results

Eleven included patients received HSCT for CMH class II deficiency (n= 2), Wiskott Aldrich syndrome (n= 2), chronic granulomatous disease (n=1), Interferon-gamma receptor deficiency (n=1) and severe combined immunodeficiency (n= 5). BCG disease onset was prior to HSCT in 10 patients and after HSCT in one patient. Before HSCT, BCG disease was loco-regional in four patients and disseminated in six patients. Five patients had a sustained response to treatment, two patients relapsed and three patients had persistent disease. After HSCT, one patient developed regional BCG disease at one month. One patient showed persistent disseminated BCGite requiring splenectomy at 12 months post HSCT. BCG disease treatment was continued for at least 6 months in all patients with improvement in clinical signs and progressive regression of lymphadenitis. Good immune reconstitution was acheived in 10 patients without recurrence of BCG disease. One patient died from severe graft versus host disease one month after HSCT.

Conclusions

BCG disease is lethal in severe PIDs if not treated. Combined with prolonged medical therapy, HSCT has significantly improved survival once immune reconstitution was achieved.

Background and Aims

In common variable immunodeficiency disorders (CVID), splenectomy has been used mainly in refractory autoimmune cytopenia. The aim of the study is to explore circumstances and outcomes after therapeutic splenectomy in CVID.

Methods

We retrospectively reviewed two cases of CVID patients who underwent splenectomy.

Results

Case 1: A 19-year-old boy born to non-consanguineous parents, followed for CVID revealed at 16 years of age, with chronic respiratory symptoms, interstitial lung disease, lymphoproliferative syndrome, and recurrent infections. Respiratory pathology has been attributed to a granulomatous lymphocytic interstitial lung disease. He had heterogeneous splenomegaly exceeding 20 cm leading to hypersplenism and refractory cytopenia. Splenectomy was done at the age of 19 years; The pathological study showed granulomatosis. The short-term evolution was favorable.

Case2: A 42-year-old woman, followed for CVID, diagnosed at age 26, in front of the family history of CVID, episodes of recurrent skin infections, ORL (sinusitis and otitis) and respiratory (recurrent pneumopathies with obliterant bronchopathy), as well as autoimmune thrombocytopenia. Biology has shown a low level of different immunoglobulins and low B-memory-lymphocytes. The patient was splenectomized for corticosteroid-dependent autoimmune thrombocytopenia. The intervention was followed by a long-term normalization of platelet count but without a significant reduction in infections after a 20-year follow-up.

Conclusions

Splenectomy is recommended as a therapeutic option for patients with refractory cytopenias and/or autoimmunity, even though CVID patients undergoing splenectomy may be at increased risk for infection given their intrinsic immunological defects. Future trials are needed to provide clearer guidance on the second-line management.

Background and Aims

Haplo-haploidentical HSCT with post-transplant cyclophosphamide (PT-Cy) is an emerging alternative in primary immune deficiency patients without sibling matched donor (MSD). There are very few reports of haplo-haploidentical HSCT with PT-Cy in WAS patients. The aim of the study is to report the results of this technique in a WAS patient.

Methods

We report the case of a 3-year-old boy followed for a WAS. His maternal cousin received HSCT for the same disease from MSD. He presented repetitive hemorrhagic syndrome with thrombocytopenia, eczema, autoimmune anemia, and locoregional becegitis. The detection of a WASp gene mutation confirmed the diagnosis. He has no MSD, so haplo-identical HSCT was performed from his mother.

Results

Pre-transplant conditioning regimen included thymoglobulin, Busilvex, and Fludarabine. He received PT-Cy (day 3 and 4), in addition to Cyclosporine and Mycophenolate Mofetil. Graft CD34 were 3.75 106/kg. Neutrophile engraftment was achieved at day 20 post-HSCT. Chimerism showed donor cells at day 30. At day 30, he presented a severe cutaneous and digestive GVHD confirmed by biopsies. No sufficient improvement was noted after three first-line immunosuppressors. Cutaneous and digestive remission was obtained after treatment with rabbit thyroglobulin. CMV reactivation responsive to preemptive treatment occurred at day 45. Four months after HSCT, He is alive, infection free, no GVHD sign, but immune reconstitution is not yet achieved.

Conclusions

Haploidentical HSCT with PT-Cy is a new therapeutic alternative in WAS patients who do not have a MSD. However viral infections and GVHD could delay immune reconstitution and make management difficult.