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.

A number of presentations of chronic demyelinating polyneuropathy have been identified, each distinguished by its phenotypic pattern. In addition to classic chronic inflammatory demyelinating polyneuropathy (CIDP), which is characterized clinically by symmetric proximal and distal weakness and sensory loss, several regional variants can be recognized: multifocal motor neuropathy (MMN: asymmetric and pure motor), multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy (asymmetric, sensory, and motor), and distal acquired demyelinating symmetric (DADS) neuropathy (symmetric, distal, sensory, and motor). There are also temporal, pathological, and disease‐associated variants. This review describes a clinical scheme for approaching the chronic acquired demyelinating polyneuropathies that leads to a rational use of supportive laboratory studies and treatment options. In addition, we propose new diagnostic criteria for CIDP that more accurately reflect current clinical practice. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 311–324, 2001

No abstract

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.