Classic Dermatomyositis Research Articles

Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies: Common Interferon Signature but Distinct NOS2 Expression

The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5(+)-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed inanti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

Clinically amyopathic dermatomyositis: clinical features, response to medications and malignancy-associated risk factors in a specific tertiary-care-centre cohort.

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) characterized by the typical DM cutaneous manifestations but without myositis. There is a relative paucity of characterized cases of CADM in the peer-reviewed medical literature. To characterize the clinical features, response to medications and malignancy-associated risk factors of patients with CADM with available baseline data seen at a single tertiary-care centre. A retrospective review was undertaken of 44 patients with CADM with available clinical and serological data prior to onset of treatment. Patients with CADM comprised 18% of all patients with DM with baseline data available at our institution. Although the majority of patients showed improvement with the first prescribed treatment, most required additional medications to control their CADM. Six of 44 patients had an associated malignancy. Photosensitivity and periungual erythema were found to be associated with absence of malignancy (P = 0·03 and P = 0·02, respectively). Patients with malignancy-associated CADM were found to be more likely to have a cutaneous response with the first prescribed treatment than patients without malignancy (P = 0·04). CADM represents a significant subset of the DM population. As with classic DM, the cutaneous manifestations of CADM often represent a therapeutic challenge. A subset of patients with CADM has underlying malignancies, and these may differ from those typically associated with classic DM. Differences in serological abnormalities, cutaneous manifestations and response to first treatment among patients with CADM with and without malignancy were found, and suggest distinct pathophysiologies among CADM subsets. Characterization of this cohort expands the knowledge about this unique DM subset.

The Clinical and Histological Spectrum of Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of myositis, characterised by chronic muscle weakness, cutaneous features, different extra-muscular manifestations and circulating autoantibodies. IIMs included classical polymyositis (PM), dermatomyositis (DM) and other different types of myositis with a wide range of muscle involvement. A complete autoantibody profile and a muscle biopsy are mandatory to correctly diagnose different clinical entities and to define their different prognosis. Bohan and Peter's criteria included five items to diagnose adult onset PM and DM. The sensitivity was 74-100%, while the specificity is low, due to a poor ability to differentiate PM from neuromuscular diseases. Other criteria included a more accurate histological definition of PM, DM or amyopathic DM, obtaining a higher specificity. Autoantibodies' association, interstitial lung disease and clinical cardiac involvement represent the main items that could define the prognosis of these patients. On the other hand, inclusion body myositis is a different myopathy characterised by a peculiar muscle mass involvement, muscle atrophy and progressive loss of function, due to complete failure to all immunosuppressive drugs used. Treatment of IIMs is based on corticosteroids (CS), which show rapid clinical response and functional improvement. Different immunosuppressant drugs are given to obtain a better control of the disease during CS tapering dose. No controlled double blind trials demonstrated the superiority of one immunesuppressant on another. The occurrence of interstitial lung involvement requires the immediate introduction of immunosuppressants in addiction to CS. Severe dysphagia seems to improve with intravenous immunoglobulins (Ig). Physical therapy could be started after the acute phase of diseases and seems to have a beneficial role in muscle strength recovery.

Serum IL8 and mRNA level of CD11b in circulating neutrophils are increased in clinically amyopathic dermatomyositis with active interstitial lung disease.

The objective of this study is to assess serum IL8 and the potential activity of circulating neutrophils on relative messenger RNA (mRNA) levels and their relationship with disease activity in clinically amyopathic dermatomyositis (CADM) associated with interstitial lung disease (ILD). We studied 18 CADM patients and compared them with 18 classic dermatomyositis (DM) patients and 18 healthy control subjects. Serum IL8 level and mRNA expressions of neutrophils (chemokine (C-X-C motif) receptor 1 (CXCR1), cluster of differentiation molecule 11b (CD11b), cluster of differentiation 64 (CD64), myeloid cell leukemia 1 (MCL1), interleukin-18 (IL18)) were detected. The overproduction of serum IL8 level was most significant in the CADM group with active period. The mRNA expressions of CD11b, IL18, and MCL1 were greatly increased in the neutrophils in patients with CADM compared with DM or healthy controls. Up-expressions of CD11b, IL18, and MCL1 were detected in the neutrophils in CADM patients of active period compared with remission period. A positive correlation was found between CD11b mRNA level and high-resolution computed tomography (HRCT) score, in CADM associated with ILD. Serum IL8 level and mRNA levels of CD11b, MCL1, and IL18 in circulating neutrophils are related with the disease activity of CADM-ILD. The mRNA level of CD11b is positively correlated with HRCT score in CADM-ILD.

I.I.7 - Contribution of myopathological analysis to myositis classification in a multidisciplinary approach

Diagnosis of inflammatory myopathies is based on evaluation of a certain clinical syndrome, laboratory results, electromyography and the myopathological assessment of a muscle biopsy. Recently, several additional parameters have been taken into consideration; among these, serological auto-antibody testing is the most relevant. The current classification of inflammatory myopathies (IIMs) comprises polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and non-specific myositis (NSM). This classification has been a subject of intense critique at various levels. First, the entity of polymyositis has been questioned, since many of these patients developed either sIBM later on, or should better be grouped among the IMNM group or the NSM/overlap myositis group. Second, dermatomyositis encompasses a multitude of subgroups with different clinical, therapeutical and prognostic implications. It has been shown recently that certain subgroups can be defined by different myositis specific auto-antibodies, such as TIF1γ, Mi-2, NXP2 or MDA-5. Anti-TIF1γ+ and NXP2+ adult patients show an increased risk of systemic malignancy, while anti-Mi-2+ patients harbour a classical dermatomyositis with good response to treatment, and NXP2+ juvenile DM patients have a strongly increased risk of developing calcinosis. The morphology and in situ immune mechanisms of the skeletal muscle of these subentities are presented. Third, necrotizing myopathy was recently added to the IIMs; however, IMNM still comprises a heterogeneous group of diseases. Recently interesting advances have been achieved, illuminating the immunopathogenesis from anti-SRP+, anti-HMGCR+ patients and anti-synthetase syndrome-associated myositis. These entities will be discussed in the light of clinical, serological, morphological and immunological characteristics.

Renal cell carcinoma and amyopathic dermatomyositis.

Amyopathic dermatomyositis (dermatomyositis siné myositis) is a rare disorder with cutaneous lesions identical to those of classic dermatomyositis, but with no clinical evidence of myopathy. Association with malignancy has been suggested in a number of reports. We report the case of a 69-year-old man with a recent diagnosis of amyopathic dermatomyositis, who presented to the urology service with hematuria. Investigations revealed a 5.8-cm renal cell carcinoma and the patient underwent left radical nephrectomy without complication. To our knowledge, an association with renal cell carcinoma and amyopathic dermatomyositis has not been previously described.

Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis

The study aims to comprehensively assess the profiles of myositis-specific autoantibodies (MSAs) in Chinese patients with polymyositis (PM)/dermatomyositis (DM) and compare them with a Japanese cohort. One hundred forty-five Chinese patients (68 classic DM, 25 clinically amyopathic DM [CADM], and 52 PM) and 165 Japanese patients (56 classic DM, 52 CADM, and 57 PM) were recruited. MSAs were measured with immunoprecipitation, enzyme-linked immunosorbent assay, or immunoprecipitation-immunoblotting. MSA frequencies were compared. The overall frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was significantly higher in the Chinese patients than in the Japanese cohort (36.6 % [53/145] versus 15.8 % [26/165], respectively, P < 0.001), whereas the frequencies of anti-signal recognition particle (SRP) antibodies (1.4 % [2/145] versus 7.9 % [13/165], respectively, P = 0.008) and anti-aminoacyl-transfer RNA synthetase (anti-ARS) antibodies (27.6 % [40/145] versus 40 % [66/165], respectively, P = 0.02,) were significantly lower. The significantly lower frequency of anti-ARS antibodies and significantly higher frequency of anti-MDA5 antibodies in the Chinese patients were observed in the classic DM subset (14.7 % [10/68] versus 46.4 % [26/56], respectively, P < 0.001, and 45.6 % [31/68] versus 5.4 % [3/56], respectively, P < 0.001) and CADM subset (8.0 % [2/25] versus 28.8 % [15/52], respectively, P = 0.04, and 88.0 % [22/25] versus 44.2 % [23/52], respectively, P = 0.0002), but not in the PM subset. The first detailed profile of MSAs in Chinese patients with PM/DM was established. The differences in MSA frequencies in the Chinese cohort and Japanese cohort suggest underlying genetic and/or environmental differences between these two populations. Key Messages • A significantly higher frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was observed in Chinese patients with polymyositis/dermatomyositis (PM/DM) than in Japanese patients. • Our findings suggest that distinct genetic and/or local environmental factors affect Chinese and Japanese patients with PM/DM, who have been considered a "homogeneous" population in previous studies.

G.P.71: Inflammatory myopathy associated with anti-MDA5 antibodies: A new entity?

The anti-MDA5 auto-antibody (Ab) is specifically associated with a subgroup of dermatomyositis patients. Patients suffer from mainly extramuscular involvement (lung and skin) whereas clinical signs of myopathy are rather mild or absent. Although extra muscular lesions are well described, there are no reports about the affection of the muscle in terms of morphology and immunology. To describe the histological pattern of the skeletal muscle and the intrinsic immune response. Immunohistochemical analysis and molecular testing of a comprehensive panel of mediators involved in the immune response were performed by quantitative PCR (n=10). Histological analysis were performed using imageJ software on digitally completely scanned slides. Results are compare to patients with classical dermatomyositis (cDM) based on ENMC criteria (<i>n</i>=7). Only 6 patients had a muscular deficit (the mean MRC score of the weakest muscular group was 4.5±0.5) and CK level was normal in 6 patients (mean CK level was 498±809 I.U/l). Histological analysis showed that patients do not present the classical feature of perifascicular fiber atrophy. All, but one had inflammation (focal and located in perivascular regions). Compared to cDM patients inflammatory infiltrates were significantly less intense (CD45+cells 35.8±28 vs. 5.9±7.6cells/mm²; <i>p</i><0,05). MHC-I over-expression was also less intense and more focal compared to a diffuse over-expression with a perifascicular emphasis in cDM patients (2.5±1.2 vs. 4.7±0.4, <i>p</i><0.05). In cDM patients, capillary density is reduced (278±40 vs. 340±022, <i>p</i>=0.05), frequency of enlarged capillaries however is increased (14±6.8% vs. 5.8±3.3, <i>p</i><0.05) and endothelial tubuloreticular inclusions were observed in only half of anti-MDA5 Ab-positive patients. Anti-MDA5 Ab positive patients present a distinc pattern compared to cDM patients in line with the clinical observation. Nevertheless we do not know yet, if it is an attenuated form of cDM or a separate entity.

Comparison of radioimmunoprecipitation versus antigen-specific assays for identification of myositis-specific autoantibodies in dermatomyositis patients

Background. To confirm the antigen specificities of autoantibodies that precipitate 140-kDa (anti-p140) or 155/140-kDa polypeptides (anti-p155/140) previously identified by radioimmunoprecipitation in Korean patients with dermatomyositis (DM) and to look into the relationship between each MSA and clinical features of DM.Methods. Seventeen serum samples of classic DM patients who had been found to have either anti-p140 antibodies (n = 9) or anti-p155/140 (n = 8) antibodies in our previous study were examined using enzyme-linked immunosorbent assay (for anti-MDA5 antibodies) and immunoblotting (for anti-MJ/NXP-2 and anti-TIF-1γ antibodies).Results. Seven out of nine anti-p140 antibody positive patients were found to have anti-MDA5 antibodies. Two out of nine had anti-MJ/NXP-2 antibodies with no interstitial lung disease (ILD). All eight anti-p155/140 antibody positive patients were found to have anti-TIF-1γ antibodies. Anti-TIF-1γ and anti-MDA5 antibodies were simultaneously detected in one patient with anti-p155/140 antibody, who suffered HIV infection and non-Hodgkin's lymphoma. The associations between anti-MDA5 antibody and rapidly progressive ILD and between anti-TIF-1γ antibody and cancer-associated DM were confirmed to be significant.Conclusions. Although radioimmunoprecipitation still looks to be a good screening tool, confirmation with antigen-specific assays seems mandatory. The associations between anti-MDA5 and rapidly progressive ILD and between anti-TIF-1γ and cancer-associated DM were confirmed in Korean patients with DM.

The clinical features, diagnosis and classification of dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by an inflammatory infiltrate primarily affecting the skeletal muscle and skin. Most common and peculiar cutaneous lesions include Gottron's papules, Gottron's sign and heliotrope rash. Different DM subsets have been identified until now encompassing classic DM, amyopathic DM, hypomyopathic DM, post-myopathic DM, and DM sine dermatitis.Patients with DM have a higher incidence rate of malignancy than the normal population. In these patients cancer occurs in about 30% of cases with higher occurrence in men and in elderly people.Bohan and Peter's diagnostic criteria, proposed in 1975, have been widely accepted and used until now. In the last ten years muscle immunopathology, myositis specific autoantibodies testing, and the use of new techniques of muscle imaging such as contrast-enhanced ultrasound or Magnetic Resonance Imaging have been introduced in the diagnostic work-up of patients with DM leading to the development of new diagnostic criteria.

Auto-anticorps au cours des myosites

Patients suffering from muscular symptoms or with an increase of creatine kinase levels may present a myopathy. In such situations, clinicians have to confirm the existence of a myopathy and determine if it is an acquired or a genetic muscular disease. In the presence of an acquired myopathy after having ruled out an infectious, a toxic agent or an endocrine cause, physicians must identify which type of idiopathic myopathy the patient is presenting: either a myositis including polymyositis, dermatomyositis, and inclusion body myositis, or an immune-mediated necrotizing myopathy. Histopathology examination of a muscle biopsy is determinant but detection of autoantibody is now also crucial. The myositis-specific antibodies and myositis-associated antibodies lead to a serologic approach complementary to the histological classification, because strong associations of myositis-specific antibodies with clinical features and survival have been documented. The presence of anti-synthetase antibodies is associated with an original histopathologic pattern between polymyositis and dermatomyositis, and defines a syndrome where interstitial lung disease drives the prognosis. Anti-MDA-5 antibody are specifically associated with dermatomyositis, and define a skin-lung syndrome with a frequent severe disease course. Anti-TIF1-γ is also associated with dermatomyositis but its presence is frequently predictive of a cancer association whereas anti-MI2 is associated with the classical dermatomyositis. Two specific antibodies, anti-SRP and anti-HMGCR, are observed in patients with immune-mediated necrotizing myopathies and may be very useful to distinguish acquired myopathies from dystrophic muscular diseases in case of a slow onset and to allow the initiation of effective therapy.

Clinical Phenotype of Japanese Patients with Dermatomyositis—Classification Based on Dermatomyositis-Specific Autoantibodies

Objectives: To correlate the precise specificity of autoantibodies in Japanese dermatomyositis (DM) patients with their clinical phenotypes. Methods: Serum samples from 94 adult DM patients (67 with classical DM and 27 with clinically amyopathic dermatomyositis, CADM) were screened for autoantibodies using immunoprecipitation assays. Patients with antibodies against aminoacyl transfer RNA synthetase (ARS), Mi-2 or who had other autoantibodies were assessed for clinical symptoms and laboratory findings. Results: Sera from 27 of 94 DM patients (29%) were found to have anti-ARS antibodies. Nineteen (20%) had anti-CADM-140/MDA5, 5 (5%) had anti-Mi-2, and 8 (6%) had anti-p155/TIF1-γ. Anti-MJ/NXP-2 was not found in our series of adult DM. Seventeen patients with anti-ARS had fever and 22 had arthritis and interstitial lung disease (ILD), compatible with a diagnosis of anti-ARS syndrome. Seventeen of 19 (89%) with anti-CADM-140/MDA5 had ILD, 16 (84%) of whom developed rapidly progressive ILD (RP-ILD). Four of 5 (80%) with anti-Mi-2 had heliotrope rash and/or Gottron’s sign/papules, and 2 (40%) had V-sign and/or shawl-sign rash, whereas no ILD or malignancy was detected. As seen with anti-Mi-2-positive patients, a low frequency of ILD (13%) was found in patients with anti-p155/TIF1-γ but 6 of 8 (75%) had malignancy during their course. The frequency of ILD was significantly higher in patients with anti-ARS or anti-CADM-140/MDA5 compared with anti-Mi-2 or anti-p155/TIF1-γ (81% and 89%, respectively). It should be noted that anti-CADM-140/MDA5-positive patients suffered significantly more RP-ILD compared to patients with anti-ARS (84% vs. 7%, P < 0.0001). On the other hand, anti-p155/TIF1-γ positive patients had a significantly higher rate of malignancy compared with anti-ARS-, anti-CADM-140/MDA5-and anti-Mi-2-positive patients (75% vs. 7%: P = 0.0004, 5%: P = 0.0006, 0%: P = 0.02, respectively). Conclusions: These results indicate that in addition to antibodies previously identified as specific for DM, autoantibodies newly found in these patients are useful for stratifying them into clinical subgroups.

The Myositis Autoantibody Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, “shawl-sign” rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and “mechanic’s hands,” and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes.

AB1167 Differences and similarities in clinical manifestations and survival between adult-onset and childhood-onset patients with idiopathic inflammatory myopathies

BackgroundIdiopathic Inflammatory Myopathies (IIM) comprise an heterogeneous group of systemic diseases, with an important morbidity and mortality, depending on different age of onset.ObjectivesTo study clinical manifestations, survival and causes of...

AB0508 Clinically amiopathic dermatomyositis: comparison with classical dermatomyositis and description of clinical outcome

BackgroundClinically amiopathic dermatomyositis (CADM) is characterized by the presence of dermatological features similar to DM without clinical signs of muscular involvement. CADM is further distinguishable in amiopathical DM (ADM) and...

Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease

Objectives: We examined the relationship between disease activity and anti-CADM-140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA).Methods: Sera from 63 patients with dermatomyositis (DM) [46 classic DM, 17 clinically amyopathic DM (CADM)] were screened for autoantibody using immunoprecipitation assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti-CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and clinical course or outcome were analyzed.Results: Sera from 14 patients with DM (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti-CADM-140/MDA5 before treatment was significantly lower in patients who responded to therapy and survived (responder group, n = 4) than in those who did not respond and died (nonresponder group, n = 6) (110.3 vs. 356.9, P = 0.019). In the responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased down to below the cutoff level after treatment (n = 3, 113.4 vs. 1.6, P = 0.033), whereas that of the nonresponder group did not decrease sufficiently and sustained high level (n = 4, 372.5 vs. 198.4, P = 0.31).Conclusions: These results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels to predict outcomes of RP-ILD as well as to monitor disease activity in patients with DM and RP-ILD.

Dysregulation of the type I interferon system in adult‐onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease

It has been speculated that viral infection might be one of the potential aetiologies for adult-onset clinically amyopathic dermatomyositis (CADM). The molecular pathogenesis remains largely unknown. To explore whether dysregulation of the type I interferon (IFN) system is involved in the pathogenesis of CADM. We studied 16 patients with CADM and compared them with healthy control subjects (n = 20) and patients with classic dermatomyositis (DM, n = 16) and polymyositis (PM, n = 16). Expressions of mRNA for serial toll-like receptor genes (TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9) and type I IFN-regulated genes (IRF7, ISG15 and MxA) in peripheral blood leucocytes (PBL) were detected by real-time polymerase chain reaction analysis. The level of IFN-α in blood was tested by enzyme-linked immunosorbent assay. The mRNA expressions of TLR7, TLR9 and IRF7 were greatly elevated in the PBL from patients with CADM compared with controls. Upregulation of the ISG15 and MxA genes was detected in the PBL from patients with CADM, as well as from patients with classic DM. Among the four study groups, the overproduction of IFN-α in blood was most significant in the CADM group. Especially, IFN-α level was obviously high in the clinical interstitial lung disease (ILD) subgroup of patients with CADM. Positive correlations were found between IFN-α concentration and other unfavourable prognostic factors of CADM-associated ILD. Our data suggest that the dysregulation of the type I IFN system may be implicated in CADM pathogenesis. IFN-α may be a useful biomarker for assessing the disease severity of CADM-associated ILD.

A Novel Dermato-Pulmonary Syndrome Associated With MDA-5 Antibodies

Melanoma differentiation-associated protein 5 (MDA-5) is a novel autoantibody frequently characterized by interstitial lung disease and a distinct cutaneous phenotype with palmar papules, ulceration, and rash. Virtually all patients have underlying dermatomyositis, but many lack the characteristic clinical myopathy associated with it. In the setting of amyopathic disease, the absence of clinically available biomarkers or clear pathologic diagnosis can complicate effective prognostic and therapeutic intervention. Until recently the presence of MDA-5 antibody associated dermato-pulmonary syndrome was described only in Asian populations. We present 2 cases of MDA-5-associated dermato-pulmonary syndrome and provide a comprehensive review of available literature.

Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease

We examined the relationship between disease activity and anti-CADM-140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA). Sera from 63 patients with dermatomyositis (DM) [46 classic DM, 17 clinically amyopathic DM (CADM)] were screened for autoantibody using immunoprecipitation assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti-CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and clinical course or outcome were analyzed. Sera from 14 patients with DM (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti-CADM-140/MDA5 before treatment was significantly lower in patients who responded to therapy and survived (responder group, n = 4) than in those who did not respond and died (nonresponder group, n = 6) (110.3 vs. 356.9, P = 0.019). In the responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased down to below the cutoff level after treatment (n = 3, 113.4 vs. 1.6, P = 0.033), whereas that of the nonresponder group did not decrease sufficiently and sustained high level (n = 4, 372.5 vs. 198.4, P = 0.31). These results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels to predict outcomes of RP-ILD as well as to monitor disease activity in patients with DM and RP-ILD.

Hydroxyurea‐induced dermatomyositis: true amyopathic dermatomyositis or dermatomyositis‐like eruption?

Hydroxyurea-induced dermatomyositis is a rare adverse reaction of long-term hydroxyurea therapy. It has been reported under different names; however, the exact classification and nomenclature of this eruption have been the subject of much debate, and a more precise term is still awaiting. Herein, we review the different aspects of this reaction and suggest a new term that might help to minimize the confusion about its nomenclature. We describe a 68-year-old woman who had been on long-term hydroxyurea therapy for the treatment of chronic myeloid leukemia for nine years. She presented with typical dermatomyositis-like lesions and many of the other mucocutaneous adverse effects of hydroxyurea. Skin examination revealed typical Gottron's papules on the dorsa of the hands, atrophy, xerosis, acquired ichthyosis, photosensitivity, cutaneous, oral and nail hyperpigmentation, acral erythema, palmoplantar keratoderma, actinic keratoses, and leg ulcers. There was no clinical or laboratory evidence of proximal muscle weakness. Cessation of hydroxyurea was associated with remarkable improvement of the skin lesions. Hydroxyurea-induced dermatomyositis is a rare drug-induced dermatomyositis characterized by skin lesions identical to classic dermatomyositis without clinical or laboratory evidence of myositis. We propose that the term hydroxyurea-induced amyopathic dermatomyositis that adequately describes the findings reported in this subset of patients would be more precise and specific.