Granulomatous inflammation in cartilage-hair hypoplasia: Risks and benefits of anti–TNF-α mAbs

Foetal presentation of cartilage hair hypoplasia with extensive granulomatous inflammation

“…A similar observation was initially reported 50 years ago in a female infant with severe combined immunodeficiency and shortlimbed dwarfism [14]. More recently, four other cases of granulomatous inflammation involving the skin and some visceral organs have been identified from a cohort of 21 patients with CHH [15]. Granulomas have also been described in patients with other immunodeficiency syndromes, e.g., common variable immunodefiency, T-cell immunodefiency, inflammatory disorders (Crohn disease and sarcoidosis), and chronic granulomatous disease.…”

Granulomatous inflammation: The overlap of immune deficiency and inflammation

“…In addition to increased susceptibility to infections, these patients can present a broad range of symptoms such as autoimmunity, granulomatous inflammation, lymphoproliferation, and increased risk of malignancy [66,67]. Granulomatous inflammation has been reported in patients with various genetic defects (Table 5), mainly hypomorphic recombination-activating gene (RAG) mutations [68], hypomorphic Artemis deficiency [69], hypomorphic JAK3 deficiency [70], CD40L deficiency [71], ataxia telangiectasia [72], Nijmegen breakage syndrome [73], cartilage hair hypoplasia [74], and lipopolysaccharideresponsive beige-like anchor (LRBA) deficiency [75]. It has also been reported in a patient as a complication of low immune reconstitution after a haploidentical hematopoietic stem cell transplantation (HSCT) for an X-linked SCID [76].…”

“…Histopathologic features of granulomatous lesions are heterogenous [68,74]: there could be (i) sarcoidosis-like granulomas, mainly composed of epithelioid cells associated with few lymphocytes and giant cells arranged in well-circumscribed nodules, (ii) poorly defined tuberculoid granulomas with numerous giant multinucleated cells associated with some lymphocytes and few epithelioid cells, and (iii) histiocytic palisading granulomas with a central necrobiotic area. Immunohistologic staining showed that macrophages and epithelioid cells are CD68þ while lymphocytes are predominantly CD8þ.…”

Advances in basic and clinical immunology in 2011

“…The investigators also showed that the use of etanecept in this animal model of granuloma did not reduce the granuloma size, and that TNF-α deficient and CGD double knockout mice produced a similar inflammatory response than CGD mice, suggesting that the role of TNF-α might be negligible. The use of anti-TNF-α antibodies for granulomatous diseases was similarly addressed by Moshous et al 54 in CHH patients. Four of 21 CHH patients had cutaneous and subcutaneous granulomatous infalmmation and were treated with infliximab, resulting in partial regression in 3 cases.…”