Cutaneous and systemic granulomatosis in ataxia-telangiectasia: a clinico-pathological study

Abstract

Introduction: The development of granulomas is a well-recognized manifestation of immunodeficiency in ataxia-telangiectasia (A-T), resulting from lymphocyte developmental abnormalities, impaired immunosurveillance, and inappropriate innate immune response-driven inflammation.

Aim: To better understand pathological and immunological phenomena involved in development of cutaneous and visceral granulomatosis observable in patients with ataxia-telangiectasia.

Material and methods: We retrospectively reviewed medical records of eight A-T children, aged from 2 to 13 years, with regard to clinical, immunological and histopathological features of cutaneous and visceral granulomatosis.

Results: In four out of eight A-T patients studied, cutaneous granulomas clinically presented as skin nodules and ulcerated erythematous plaques disseminated on the face, and on trauma-prone areas of upper and lower extremities. Visceral granulomatosis had a severe clinical course and involved the lungs, the spleen, the liver and the larynx. Histologically, cutaneous and laryngeal granulomas showed extensive cellular infiltrations containing T lymphocytes with predominating CD8+ phenotype and with CD68+ histiocytes. The immunological profile with the hyper-IgM phenotype, markedly reduced numbers of B and naive CD4+ and CD8+ T cells with predominating IgM-only memory B cells and skewed repertoire of a T cell receptor was observable in patients with skin and visceral granulomatosis.

Conclusions: In the setting of combined immunodeficiency in A-T, cutaneous and systemic granulomatosis reflects a granulomatous reaction pattern, as a result of inappropriate immune regulation.

Keywords: ataxia-telangiectasia; children; granuloma; immunodeficiency; lymphopenia.

Figure 1

A – An MRI of the abdominal cavity and the retroperitoneal space with contrast medium, transverse section, showing a markedly enlarged spleen (its dimensions 17.3 × 8.5 cm, length x width, respectively) with non-homogenous nodular remodelling of its parenchyma. These numerous infiltrates of different size (from 5 to 60 mm) exhibit hypointense signals in T1 and T2- dependent sequences. B – An MRI of the chest with contrast medium, transverse section, showing mediastinal and perihilar lymphadenopathy and numerous small (size from 4 to 6 mm of a diameter) perilymphatic nodules, localized subpleurally and surrounding bronchovascular bundles. In the right middle lobe (segment 5) pericardial consolidations in the lung parenchyma with fibrotic strands, accompanied by irregular thickening of the peribronchium of the bronchial tree and peripheral bronchiectases are visible. C – An MRI of the neck, without contrast medium, frontal section, showing a thickening of the glottis, the aryepiglottic folds, the vestibular folds, and the vocal cords. At the level of the laryngeal inlet and upper part of the vestibule, the patency of the larynx is significantly reduced (to 2 mm of a diameter) with a slit-like upper part of the piriform sinus. In the oropharynx, hypertrophy of the lymphoid tissue is visible

Figure 2

A – Tuberoid deformations of the fingers. B – Extensive, exophytic, scarred granulomatous lesions in the area of the elbow joint. C – Ulcerated, crusty and bleeding lesions of the knee