Background and Aims

Late onset combined immune deficiency (LOCID) is recently described in patients with previous infection indicative of a severe defect in cell-mediated immunity and/or low CD4+ cell counts. This disease can occur at any age and it is extremely heterogeneous. Authors present here two new observations.

Methods

We describe the diagnosis of LOCID in two patients followed in the pediatric immune-­hematology unit.

Results

Case1: A 59-year-old woman with a history of B lymphoma diagnosed after two episodes of deep vein thrombosis and lower respiratory tract infections leading to bronchiectasis and postinfectious obliterating bronchopathy. The diagnosis of LOCID was retained in front of hypogammaglobulinemia (IgG=0.17g/L, IgA=0.02g/L , IgM=0.1g/L), B-lymphocytes at 1% and criteria of profound T cell deficiency (Lymphocytes=1000/mm3, CD4+ at 15.5% and CD4 naive at 4%).

Case2: A 22-year-old girl, from non-consanguineous parents, with family history of early death. In her past medical history, the patient had celiac disease with Evans syndrome at 12 years old. LOCID was suspected in front of the association of infectious episodes: oral candidiasis, recurrent upper and lower respiratory tract infections with bronchiectasis, hemi-corporal zona with severe retinal zoster and splenomegaly. Immunity exploration found hypogammaglobulinemia (IgG=3.4g/L, IgA=0.15g/L, IgM=0.2g/L) and 1%B lymphocyte count, decreased switched memory B cells , CD4+ at 25% (440/mm3).

Both patients responded to polyvalent immunoglobulin and anti-infectious prophylaxis (1 and 6 years follow-up, respectively) without evidence of immune reconstitution.

Conclusions

LOCID is still underdiagnosed. The main differential diagnosis is common variable immunodeficiency(CIVD). Systematic T cell phenotype may help to discriminate such patients from those with CVID.

Background and Aims

Netherton syndrome is an inherited, autosomal recessive skin disease characterized by ichthyotic erythroderma, characteristic hair anomaly (trichorrhexia invaginata), growth retardation and atopic manifestations. Authors will describe the clinical characteristics and diagnosis of Netherton syndrome.

Methods

In this report, we present 4 cases of Netherton syndrome (2 girls and 2 boys) who were consulted at an average age of 22 months for the extent of erythroderma and infectious events. The diagnosis of Netherton Syndrome was established by immunohistochemistry.

Results

Consanguinity was found in one case. The average beginning age of symptoms was 14 months with non-blistered pruritic erythroderma (n=4), itchy skin (n=4), growth retardation (n=2), recurrent ear infection (n=1), bamboo hair (n=1), signs of atopy (n=2) and sepsis (n=1). The IgE level is high in two cases (sex ratio=0.5). The clinical differential diagnosis essentially included Ommen syndrome and Netherton syndrome. Immunohistochemistry showed a LEKTI deficiency that confirmed the diagnosis of Netherton syndrome.

In all cases, therapeutic support was based on the treatment of infectious events and symptomatic skin treatment with emollients and antihistamines. Three children died and the other was lost sight of.

Conclusions

Netherton syndrome is a very rare severe immune deficiency with erythroderma and recurrent infections. Immunohistochemistry of LEKTI protein allows a fast diagnosis.

Background and Aims

Selective IgM deficiency (IGMD) is defined as serum IgM levels below 2 SD of mean with normal serum IgG and IgA. IGMD can be associated with severe and/or recurrent infections, atopy and autoimmunity.

Objective: to describe the clinical and biological aspects of IGMD.

Methods

This is a retrospective study over a 14-year period (2005 to 2019) including patients with selective IGMD followed within the National Center of Bone-Marrow Transplant of Tunisia.

Results

Eight patients were enrolled ( 4 males and 4 females). Consanguinity was found in five cases. Median age at diagnosis was 66 months (3 months, 14 years). Revealing signs were mostly infectious in six cases: bronchopulmonary infectious (n=6), upper and lower respiratory tract infections (n=4), skin infection with pseudomonas aeroginosa affecting the vulva and inguinal region (echthyma gangrenosum) (n=1). Tow patients had both infections and atopy. Other symptoms infections were hypotrophy (n=3) and hepatosplenomenomegaly (n=1). The two other cases presented isolated autoimmune manifestations: the first developed autoimmune haemolytic anemia and the second had an Evans syndrome.

The mean serum IgM level was 0,33 g/l (range 0,23-0,47). Mean serum levels of other immunoglobulins and IgG subclasses were normal. Lymphocytes immunophenotyping and lymphoblastic proliferation assays were normal.

Conclusions

Selective IgM deficiency is a rare type of Predominantly antibody deficiencies. It was characterized by isolated low levels of serum IgM. The clinical spectrum is broad, essentially associating infectious and autoimmune manifestations

Background and Aims

Ataxia-telangiectasia (AT) is an autosomal recessive disease that associates combined immunodeficiency with progressive cerebellar ataxia. It is characterized by cerebellar ataxia, oculocutaneous telangiectasia, increased susceptibility to infections, hypersensitivity to radiation and predisposition to malignancy. The aim of this observation is to describe leukemia therapeutic features in AT.

Methods

We present a patient with AT complicated by acute leukemia followed in the pediatric immune-­hematology unit. The diagnosis and management of Leukemia were retrospectively analyzed.

Results

B.I. was followed of AT since 5-year-old. She has been regularly substituted by intravenous immunonoglobulin in addition to anti-infectious prophylaxis. At 14-year-old, she developed acute non-hyperleucocytic T-lymphoblastic leukemia without meningeal involvement. She was treated according to the EORTC58081 protocol (modified). She was allocated to the Avereage Low Risk group (AR1) instead of Average High Risk (AR2). A good response to the prophase was obtained. Induction chemotherapy drugs was decreased (Vincristine from 1.5mg/m² to 0.7mg/m² and Daunorubicine from 30 to 10mg/m²). Despite this, the protocol was suspended for 15 days from the 12^th day of induction due to severe liver cytolysis and cholestasis. The patient didn’t present medullary aplasia. Chemotherapy was interrupted again at the 28^th day of induction because of fever and refractory hypoxemia. She was treated with broad-spectrum antibiotic. She died at 47 days of the beginning of chemotherapy. The post mortem bone marrow aspiration showed a complete remission of leukemia.

Conclusions

Patients with AT present chromosomal instability due to a DNA repair disorder. This may explain severe chemotherapy side effects even at low doses.

Background and Aims

Hermansky Pudlak syndrome type 2 is a rare autosomal recessive disorder resulting from functional mutations in the adaptor related protein complex 3,B1 subunit (AP3B1) gene. It is characterized by severe neutropenia, ocular albinism, interstitial pulmonary fibrosis, hemorrhagic diathesis and an absence of platelet dense granules.We describe a new case

Methods

Authors describe the phenotypic diagnosis and management of Hermansky Pudlak type 2 Syndrome in a patients followed in the pediatric immune-­hematology unit, Tunis.

Results

CM was a 8--year-old girl born from 2^nd consanguineous parents with family history of death of her sister at 7 –year-old in the context of respiratory distress and malignant varicella. The diagnosis was suspected after a history of recurrent cutaneous , ORL and respiratory infections, an episode of pneumocystis Jirovecii pneumonia and bleeding tendency with gingival bleeding and bruising. Clinical examination showed oculocutaneous albinism and finger clubbing. CBC reveal neutropenia (570/mm³) and normal platelet count. Bone marrow aspiration showed normal myeloid maturation. CT scan of the chest demonstrate pulmonary fibrosis with bilateral infiltrative lung disease. Diagnosis of HPD2 was retained in front of: Partial albinism, recurrent infections, pulmonary fibrosis Increased bleeding and neutropenia. The patient received Bactrim as secondary prophylaxis, granulocyte-stimulating factor since 2018 and she has a regular medical monitoring. Restrictive ventilation disorder was stable on spirometry and there wasn’t Pulmonary Hypertension at transthoracic echocardiography (19 year follow-up).

Conclusions

Hermansky Pudlak syndrome type 2 was rare and associated with poorly prognosis related to infections and pulmonary fibrosis.