Specifically for CADM, it appears that there is another autoantibody that reacts against a 155 kDa autoantigen. Similar to the anti–CADM-140 autoantibody, the presence of this anti-155 autoantibody appears to be highly correlated with CADM and rarely with classic DM.1,15,20
Clearly, in DM there are autoantibodies that react against both endomysial and skin capillaries, causing the clinical features of the disease. The end result of the interaction between autoantibodies and antigens in these capillaries is the activation of the complement cascade.1,2,14 The process begins with the activation of C3 and ends with the formation of the MAC, C5b-9, which causes lysis of these capillaries.21 This lysis causes microinfarcts and hypoperfusion of the involved tissues, causing muscle weakness and/or cutaneous lesions. However, MAC, C3b, and C4b have been detected on the capillary walls of patients before they had clinically significant disease.12,14 In one study of 22 skin biopsy specimens taken from patients with DM, depositions of MAC were found at the dermoepidermal junction in 86% (19/22) of biopsy specimens and on the endothelium of dermal capillaries in 77% (17/22) of biopsy specimens.11 The repeated lysis of capillaries over time leads to a decrease in the number of capillaries, which is a common finding on biopsy of both muscle and skin specimens.22 Dermatomyositis muscle biopsy results commonly show fibrin thrombi inside of endomysial capillaries leading to microinfarcts of portions of the fascicles or the periphery, resulting in perifascicular atrophy. This histologic finding is diagnostic for DM, even in the absence of inflammation.14
Our patient demonstrated a dramatic thrombotic and focally necrotic vasculopathy that is unusual for DM or CADM but has been previously reported in both.9,23 However, necrotic vasculopathy may not always be associated with an underlying malignancy. In fact, one study found that of 30 patients with both DM and a malignancy, only 2 had necrotic lesions on their body.24
Malignancy and DM—It has been proposed that there is a notable correlation between DM and the presence of an underlying malignancy4,14,18,25-28; patients with DM have a higher risk of dying from a malignancy than the general population.3 Studies have placed the co-prevalence of DM and cancer at 20% to 30%.29,30 In retrospective studies only, patients with DM have been compared with healthy cohorts to calculate a standardized incidence ratio (SIR) for the occurrence of malignancies in both groups. The SIR for all cancers in groups of patients with DM has been found to be 3.0 to 7.7 (P<.05). This correlation does not appear to be as prominent in other myositides.4,18,27,28
The cause-and-effect relationship between DM and cancer also is unclear, as patients have been diagnosed with malignancies both before and after they were diagnosed with DM.4,18 Other confounding variables, such as poor detection methods for occult malignancies, an immunocompromised state, and the use of immunomodulatory drugs to treat DM,26,28,30,31 make it even more difficult to ascertain if DM causes malignancies or vice versa. In one study of 618 patients with DM, 198 patients had cancer, of which 115 patients developed cancer after being diagnosed with DM, suggesting that DM is a risk factor for developing cancer.4 However, other studies have found that the severity of a patient’s DM will decrease if their malignancy is surgically removed29,31 and exacerbations of DM could be used to gauge recurrences of a malignancy,29 indicating that DM is a paraneoplastic process that occurs after the malignancy has emerged. Thus, it is possible that the temporal relationship of the diagnoses of DM and cancer exists as it does because the first clinical findings are those of DM, prompting the patient to seek care.
Some authors believe there is no connection between the two, claiming that the increased incidence of cancer in patients with DM is due to increased vigilance, leading to detection bias, which is indicated by the disparity in the SIR of cancer between the first year of diagnosis of DM and subsequent years. In one study, the SIR for cancer during the first year after diagnosis of DM was 26 (95% confidence interval [CI], 12-48).27 Another study noted a relatively high SIR for cancer during the first year after diagnosis but then a slow decrease in incidence in the following years.28 Some researchers believe it is a self-perpetuating phenomenon; that is, clinicians who believe there is an increased risk for malignancy will conduct a more thorough cancer workup in their patients with DM and therefore will find more malignancies.28,32 Also, many of the studies previously mentioned here were retrospective, so the case controls likely did not undergo the same extensive cancer workups as the participants with DM. There is at least one study reporting that there is no link between DM and cancer,32 but this study involved smaller patient populations and combined patients with polymyositis and DM into one cohort. This combination would have the effect of diluting the incidence of malignancy because patients with polymyositis do not have the same risk for malignancy as patients with DM.3,14,27