Background and Aims

Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, immunodeficiency, chronic pulmonary disease and chromosomal instability. Cutaneous granulomas are a known phenomenon in A-T but extra-dermal manifestation of granulomas at lymphoreticular system and lung has not been reported so far.

Methods

The clinical presentation, immunological findings, the course and discussion of potential treatment options of one patient will be reported.

Results

Here we report an A-T (c.6573-9G>A; c.8319ˍ8323dup) patient 6 years old with lymphadenopathy, splenomegaly, hepatomegaly, increasing pulmonary nodules ( from few millimeters to 1 centimeter in 6 months) (images 1-4) without respiratory symptoms. Immunoglobulin serum levels were: IgG 811 mg/dl (replacement on going: 600 mg/kg s.c.), IgA 32 mg/dl, IgM 1750 mg/dl, low CD4, absent CD4CD45RA ad low CD8. The biopsy of laterocervical lymph node showed a non-necrotizing follicle hyperplastic and granulomatous lymphadenopathy. No infection agents (mycobacteria, pneumocistys, fungi, CMV, EBV and HHV8) in the lymph node and in the bronchoalveolar lavage (BAL). We decided to perform an MRI of the lung after 3 months. A lung biopsy and all potential treatments are under discussion (steroids and monoclonal antibodies).

Conclusions

Little is known about the clinical presentation, course and treatment of granulomas in A-T; this is the first report of extra-dermal manifestation of granulomas lymphoreticular system and lung. In recent years new insight have been generated into granulomatous inflammation, this have made possible the increasing numbers of therapeutic agents targeting immune pathways, but actually there is no standard treatment

Background and Aims

Primary immunodeficiency disease (PID) is an inborn error of the immune system, and is characterized by not only susceptibility to infection but also frequent combination with autoimmune diseases and malignancies, that may be the initial presenting symptom irrespective of a previous history, making the diagnosis a challenge.

Methods

We present a patient with multiple cytopenias as the first manifestations of a Artemis deficiency.

Results

Two years-old child came to our observation for severe hemolytic anemia. After administration of Rituximab, started four months after onset due to corticodependence, we observed a failed recovery of CD20 and a persistent hypogammaglobulinemia (normal B lymphocytes at pre-rituximab immunophenotyping).

At the age of 4, he developed an autoimmune thrombocytopenia responsive to treatment with IgEV and steroid therapy. Afterwards a significant increase in infectious morbidity (2-3 episodes/year with hospitalization) occured, in particular a “round pneumoniae”, responsive to treatment with antifungals. NGS panel for SCID/CID was started because the lymphocyte immunophentyping reveal low TCD4+ and persistent low CD20.

At the age of five, the patient was treated for a nasopharyngeal EBV-related large cell B lymphoma and the biopsy, performed on a persistent skin lesion of the ankle, showed a cutaneous CD8+ cytotoxic T-cell lymphoma.

The genetic investigation has subsequently identified a heterozygosity composed of 2 new mutations of the ARTEMIS enzyme (DCLRE1C(ARTEMIS):207_209delGTT;541_542insG:L70del;E181fs).

The patient performed haploidentical HSCT.

Conclusions

Autoimmune cytopenias that are refractory to treatments and affect multiple cell lines, even if not associated with recurrent infections, imply the suspicion of primary immune deficency.