Dermatomyositis has been modeled as an autoimmune disease largely mediated by the adaptive immune system, including a local humorally mediated response with B and T helper cell muscle infiltration, antibody and complement-mediated injury of capillaries, and perifascicular atrophy of muscle fibers caused by ischemia. To further understand the pathophysiology of dermatomyositis, we used microarrays, computational methods, immunohistochemistry and electron microscopy to study muscle specimens from 67 patients, 54 with inflammatory myopathies, 14 with dermatomyositis. In dermatomyositis, genes induced by interferon-alpha/beta were highly overexpressed, and immunohistochemistry for the interferon-alpha/beta inducible protein MxA showed dense staining of perifascicular, and, sometimes all myofibers in 8/14 patients and on capillaries in 13/14 patients. Of 36 patients with other inflammatory myopathies, 1 patient had faint MxA staining of myofibers and 3 of capillaries. Plasmacytoid dendritic cells, potent CD4+ cellular sources of interferon-alpha, are present in substantial numbers in dermatomyositis and may account for most of the cells previously identified as T helper cells. In addition to an adaptive immune response, an innate immune response characterized by plasmacytoid dendritic cell infiltration and interferon-alpha/beta inducible gene and protein expression may be an important part of the pathogenesis of dermatomyositis, as it appears to be in systemic lupus erythematosus.
Distinguishing acquired demyelinating neuropathies by phenotype can often predict the presence of IgM kappa M-proteins, anti-MAG antibodies, and responses to immunomodulating therapy.
The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of “mast cell activation syndrome” (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a “consensus” (re-termed here as “consensus-1”). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as “consensus-2”), resembling “consensus-1” in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by “consensus-2” criteria has potential to be problematic, but underdiagnosis by “consensus-1” criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.
The functional disability caused by IBM reduces QoL, but psychosocial factors such as mood affect QoL directly and by influencing the degree to which disease severity reduces QoL. Further study should follow the effects of IBM on QoL over time and look at the influence of other psychosocial factors. Such studies may point to psychosocial interventions that may help improve QoL in IBM even if the disease itself cannot be treated.
This study highlights the challenges of proving that Cbl deficiency is the cause for PN and identifies clinical features that suggest Cbl-deficiency PN. Testing of serum metabolite levels may identify Cbl deficiency in some patients with normal serum Cbl levels.
Introduction
Causes of small‐fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor‐3 (FGFR‐3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS‐HDS) in cryptogenic SFN.
Methods
One hundred fifty‐five patients with biopsy‐proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS‐HDS and IgG vs FGFR‐3.
Results
Forty‐eight percent of SFN patients had serum antibodies, 37% with IgM vs TS‐HDS and 15% with IgG vs FGFR‐3. TS‐HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non–length‐dependent nerve pathology. Nintey‐two percent of patients with acute‐onset SFN had serum IgM vs TS‐HDS.
Discussion
Autoantibodies directed against TS‐HDS and FGFR‐3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS‐HDS may be a marker for SFN with an acute onset.
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