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Inflammation of subcutaneous tissue (panniculitis) may occur in association with tuberculosis, but so far only three cases of non-tuberculous mycobacteria-related lobular panniculitis have been reported. We describe two new cases with marked cellular immunity failure due to hypercorticism. Clinical presentation did not differ significantly from lobular panniculitis of other aetiologies. Histological samples displayed signs of lobular panniculitis and clues for mycobacteria infection with granulomatous lesions and presence of numerous acid-fast bacilli on special staining. Both patients responded quickly to a combination of macrolides, ethambutol and fluoroquinolones. However, like in other infections with tuberculous or non-tuberculous mycobacteria, long-term treatment (at least 6 months) was necessary to prevent relapses.