Clinical history: 78 year old woman with 20-year history of progressive weakness in lower back and thighs, and 2-year history of dysphagia with difficulty projecting voice. Patient has difficulty climbing stairs, rising from sitting/squatting.
What is the diagnosis?
Granulomatous myositis with type 2 fibre atrophy
In addition to the granulomas in the muscle biopsy, there is a general granulomatous distribution of inflammatory infiltrate. The granulomas contain multinucleate giant cells. This condition is most likely linked to sarcoidosis – the most common cause of granulomatous myositis. Some other causes of granulomatous myositis are infectious, Crohn’s disease, graft-versus-host disease, and lymphoma.
In this case, microbiological stains (Ziehl-Neelson, Gram, Grocott, PAS, PAS-D) revealed no micro-organisms. The complete clinical picture does not point to Crohn’s, graft-versus-host disease, or lymphoma.
The granulomatous infiltrate, consisting of lymphocytes and macrophages, is distributed in the peri- and endo-mysium. There is no vasculitis. The myosin ATPase stain shows atrophy of all type 2 fibres.
Sarcoidosis is a systemic disease that is characterised by the presence of non-caseating granulomas in any or many organ systems. Its clinical presentation may vary considerably; nearly any organ system may be involved. However, hilar lymphadenopathy or lung involvement is seen in chest x-rays in greater than 90 % of cases.
The aetiology of sarcoidosis is unknown. There is some suggestion that it may be a disease of disordered immune regulation in genetically predisposed individuals who are exposed to certain environmental agents. Immunologically, the disease process of sarcoidosis is driven by CD4+ T-helper cells. Systemic increases of T-cell-derived cytokines (IL-2, INF-gamma) to promote T-cell expansion and macrophage activation, as well as localised increases in cytokines (IL-8, TNF, etc) to recruit additional T-cells, are all seen. Genetically, there seems to familial and racial clustering of cases, and association with certain HLA genotypes. Environmental factors have been argued but not definitively proven.
The world-wide incidence for sarcoidosis is 20 cases per 100,000 population. Incidence peaks in all persons aged 25-35, and again in women aged 45-65. The male to female ratio is approximately 1:2. Functional impairment results in only about 15-20 % of cases. Mortality is less than 5 % for untreated cases.
Histologically, involved tissues show non-caseating granulomas composed of aggregates of tightly clustered epithelioid histocytes, often with Langhans or foreign body-type giant cells. Remotely formed granulomas may be encased in fibrous rims or replaced by hyaline scar.
Pathologic involvement of every organ has been cited. While often asymptomatic and under-identified, occult sarcoid myositis may be indicated by muscle weakness, aches, tenderness, and fatigue.