Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings

Abstract

Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR). Ten cases of EI/NV were found. H&E slides were reviewed. PCR assays for M. tuberculosis and mycobacteria other than M. tuberculosis (MOTT) were performed. PCR did not reveal M. tuberculosis (0%) or MOTT (0%) DNA, with positive controls, indicating the reliability of the assays. Among the MOTT, cutaneous infections are most commonly caused by M. marinum. Subcutaneous tuberculoid granulomas may be seen with M. kansasii, M. marinum, M. scrofulaceum and M. avium complex. M. gordonae, M. szulgai and M. malmoense rarely cause cutaneous infections. M. simiae, M. gastri and M. asiaticum are probably not cutaneous pathogens. M. tuberculosis and MOTT DNA was not found in EI/NV. EI/NV has diverse aetiologies with varying pathogeneses leading to similar histologic changes. The cases analysed may not have had an infectious aetiology. However, in EI/NV, performance of PCR for MOTT as well as M. tuberculosis complex may still be beneficial, particularly in cases from immunocompromised hosts.

Erythema Induratum: Case Series Illustrating the Utility of the Interferon-γ Release Assay in Determining the Association with Tuberculosis

“…The presence and prominence of the latter microscopic findings tend to vary with disease duration, and no features reliably reflect underlying TB or non-TB origin. 6,8,11,12 EI/NV is thought to result from a specific T cellmediated response, or type IV delayed-type hypersensitivity reaction, to an antigenic stimulus. 8,11,12 Several associations have been reported in the medical literature, with TB being, by far, the most commonly implicated trigger.…”

“…6,8,11,12 EI/NV is thought to result from a specific T cellmediated response, or type IV delayed-type hypersensitivity reaction, to an antigenic stimulus. 8,11,12 Several associations have been reported in the medical literature, with TB being, by far, the most commonly implicated trigger. 3,13 However, demonstrating the relationship between EI/NV and an underlying TB infection remains challenging as AFB stains and Mycobacterium tuberculosis cultures of skin biopsy specimens are usually negative and evidence of active systemic TB is rarely present.…”

“…Several studies have investigated PCR as a method to detect M. tuberculosis deoxyribonucleic acid (DNA) in skin biopsy specimens of EI/NV. 8,[12][13][14][15][16][17][18][19][20] The reported rates of positivity in the five largest studies were 0% (0/20), 14 14% (9 of 65), 12 25% (5 of 20), 13 75% (9 of 12), 15 and 77% (40 of 52). 16 Possible explanations for the inconsistent results included different PCR assays and geographic variation of TB frequency.…”

Explosive generalization of nodular vasculitis – Mycobacterium marinum challenges the paradigm

“…This finding challenges two current paradigms: (i) that mycobacteria other than M. tuberculosis are not present in NV/ EIB and (ii) that microbes cannot be cultivated from these lesions. 6 Instead, the idea is supported that NV represents an end stage of a successful elimination of microbes like M. marinum by the immune system. Consistent with this, PCR detects M. tuberculosis DNA in approximately 40% of EIB lesions, as putative remnants of a successful immune defence reaction.…”

Cutaneous manifestations of tuberculosis

“…A recent study carried out in northwest Spain showed that about 10% of cases of EIB were positive for M. tuberculosis by PCR 24 . Other organisms such as M. bovis 25 and Mycobacterium marinum may also be implicated 26 . Histologically, EIB is characterized by lobular panniculitis associated with vasculitis (Fig.…”