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Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets. Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules. Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity.

Objective Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE. Methods The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations. Results The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant. Conclusion We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.

The lesions of discoid lupus erythematosus (DLE) are categorized as either localized (presenting above the neck in the scalp, face, and ears), or generalized (involving areas above and below the neck, often in the upper extremities). DLE lesions are commonly incited by trauma, infection, burns, dermatitis, and ultraviolet radiation.1 Previous literature has proposed the term lupus ab igne to describe the development of clinically characteristic DLE lesions induced by chronic heat exposure.2 We present the first case, to our knowledge, of DLE lesions associated with Koebnerization from chronic heat exposure with electronic cigarette (EC) usage.

To describe diverse neurologic and neuroradiologic presentations of two rare, immunologically mediated skin conditions: Sweet disease and localized scleroderma (morphea). Core syndromes of neuro-Sweet disease (NSD) are steroid responsiveness, recurrent meningitis, and encephalitis. Focal neurologic, neuro-vascular, and neuro-ophthalmologic syndromes have been reported recently in NSD. A variety of steroid-sparing treatments and biologics have been used for relapsing NSD. Localized craniofacial scleroderma is associated with seizures, headaches, and less commonly, focal deficits and cognitive decline. Immunosuppressive therapy may be required in patients with disease progression; some refractory cases have responded to IL-6 inhibition. Our review provides an up-to-date reference for neurologists faced with a patient with a history or skin findings consistent with Sweet disease or localized scleroderma. We hope that it will stimulate collaborative studies aimed at unraveling the pathogenesis of these disorders, better characterization of their neurologic manifestations, and discovery of optimal therapeutic solutions.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy involving severe debilitation in need of diagnostics. We evaluated the proximal lower extremity musculature with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM) and dynamic DTI in DM patients and controls and compared with standard clinical workup. METHODS: In this IRB-approved, HIPAA-compliant study with written informed consent, anatomical, Dixon fat/water and diffusion imaging were collected in bilateral thigh MRI of 22 controls and 27 DM patients in a 3T scanner. Compartments were scored on T1/T2 scales. Single voxel dynamic DTI metrics in quadriceps before and after 3-min leg exercise were measured. Spearman rank correlation and mixed model analysis of variance/covariance (ANOVA/ANCOVA) were used to correlate with T1 and T2 scores and to compare patients with controls.DM patients showed significantly lower pseudo-diffusion and volume in quadriceps than controls. All subjects showed significant correlation between T1 score and signal-weighted fat fraction; tissue diffusion and pseudo-diffusion varied significantly with T1 and T2 score in patients. Radial and mean diffusion exercise response in patients was significantly higher than controls.Static and dynamic diffusion imaging metrics show correlation with conventional imaging scores, reveal spatial heterogeneity, and provide means to differentiate dermatomyositis patients from controls.• Diffusion imaging shows regional differences between thigh muscles of dermatomyositis patients and controls. • Signal-weighted fat fraction and diffusion metrics correlate with T1/T2 scores of disease severity. • Dermatomyositis patients show significantly higher radial diffusion exercise response than controls.

Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l‐arginine, which is often an effective treatment strategy in these patients. As such, l‐arginine‐based therapies should be considered in managing secondary RP, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l‐arginine in secondary RP suggest that divided dosing may begin at 1–2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l‐arginine trials to show benefit in primary RP.

Anetoderma is a rare benign elastolytic disorder that is characterized by focal loss of elastin fibers on histopathology and is often recalcitrant to treatment. We present a case of a patient with a 20-year history of pruritic and painful hyperpigmented atrophic papules clustered on the neck, axillae, inframammary folds, and right medial thigh. Although the histopathologyof her axillary lesions was consistent with anetoderma, her clinical presentation is unusual given the extent of involvement, reported pain and pruritus, and sharp demarcation of the distribution. The diagnosticuncertainty of this case led to added difficulty in management of a disease that is already notoriously difficult to treat and may significantly impact patient's quality of life.

Multiple placebo-controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP).The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined end point integrating parameters of digital blood flow and clinical severity.A systematic review was performed using MEDLINE, Embase, and the Cochrane library. Only trials comparing locally applied topical nitrates with placebo comparators were included. Studies were appraised for bias by 2 independent reviewers.A total of 7 placebo-controlled trials including 346 patients were used in the meta-analysis; 4 trials used nitroglycerin ointments, 2 used the nitroglycerin gel vehicle MQX-503, and 1 used compounded nitrite. The meta-analysis results supported a moderate-to-large treatment effect in RP (standardized mean difference [SMD] = 0.70; 95% CI, 0.35-1.05; P .0001). Subgroup analyses showed a large treatment effect in secondary RP (SMD = 0.95; 95% CI, 0.25-1.65; P = .008) and moderate effect in primary RP (SMD = 0.45; 95% CI, 0.05-0.85; P = .03).Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments.Local topical nitrates have significant efficacy in the treatment of both primary and secondary RP.

Adenosine has an important role in inflammation and tissue remodeling and promotes dermal fibrosis by adenosine receptor (A 2A R) activation. Adenosine may be formed intracellularly from adenine nucleotides or extracellularly through sequential phosphohydrolysis of released ATP by nucleoside triphosphate diphosphohydrolase (CD39) and ecto-5′-nucleotidase (CD73). Because the role of these ecto-enzymes in fibrosis appears to be tissue specific, we determined whether these ectonucleotidases were directly involved in diffuse dermal fibrosis. Wild-type and mice globally deficient in CD39 knockout (CD39KO), CD73 (CD73KO), or both (CD39/CD73DKO) were challenged with bleomycin. Extracellular adenosine levels and dermal fibrosis were quantitated. Adenosine release from skin cultured ex vivo was increased in wild-type mice after bleomycin treatment but remained low in skin from CD39KO, CD73KO, or CD39/CD73DKO bleomycin-treated mice. Deletion of CD39 and/or CD73 decreased the collagen content, and prevented skin thickening and tensile strength increase after bleomycin challenge. Decreased dermal fibrotic features were associated with reduced expression of the profibrotic mediators, transforming growth factor-β1 and connective tissue growth factor, and diminished myofibroblast population in CD39- and/or CD73-deficient mice. Our work supports the hypothesis that extracellular adenosine, generated in tandem by ecto-enzymes CD39 and CD73, promotes dermal fibrogenesis. We suggest that biochemical or biological inhibitors of CD39 and/or CD73 may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma.

Lichen myxedematosus is condition characterized by localized areas of dermal deposition of mucin, presenting with firm papules localized to few areas of the body. The condition needs to be excluded from scleromyxedema, which, in addition to the firm papular eruption, has areas of induration and is usually associated with a monoclonal gammopathyand systemic symptoms. We present a 62-year-old woman with a several-year history of asymptomatic, firm papules over the face and arms with no evidence of thyroid disease or a monoclonal gammopathy,which is consistent with a diagnosis of localized lichen myxedematosus, the discrete papular variant. The patient is being treated with a topical calcineurininhibitor.

Anetoderma is a rare benign elastolytic disorder that is characterized by focal loss of elastin fibers on histopathology and is often recalcitrant to treatment. We present a case of a patient with a 20-year history of pruritic and painful hyperpigmented atrophic papules clustered on the neck, axillae, inframammary folds, and right medial thigh. Although the histopathologyof her axillary lesions was consistent with anetoderma, her clinical presentation is unusual given the extent of involvement, reported pain and pruritus, and sharp demarcation of the distribution. The diagnosticuncertainty of this case led to added difficulty in management of a disease that is already notoriously difficult to treat and may significantly impact patient's quality of life.

Once systemic disease is in remission, it is prudent to recognize the importance of alopecia in the patient's overall sense of well-being and quality-of-life clinical outcome. Scarring alopecia (scalp discoid lupus erythematosus) can be the presenting manifestation of lupus in more than half of affected individuals. Diffuse nonscarring alopecia in lupus is usually responsive to treatment of the systemic disease. Severe, often intractable burning pruritus of the scalp is a frequent complaint in dermatomyositis. Lichen planopilaris may mimic other autoimmune forms of scarring alopecia. Alopecia can also be caused by medications used to treat systemic autoimmune disease and fibromyalgia.

Lichen planus pigmentosus (LPP) is a type oflichenoid dermatitis with superficial dermalmelanophages that presents as symmetrical,hyperpigmented macules and patches that aredistributed over the forehead, temples, cheeks, andneck. The condition most often occurs in darkerskinned individuals and is frequently resistant totreatment. Here we present a patient of Egyptiandecent with a lacy reticulated LPP eruption on theface.

Dermatomyositis is a systemic, autoimmune diseasewith a variety of clinical features that often includemyositis and characteristic cutaneous findings. Asubset of patients with dermatomyositis developcutaneous ulcers, often in the setting of vasculitis orvasculopathy. We present a case of dermatomyositiswith cutaneous ulcers that show perforatingcollagenosis on histopathologic examination.Acquired reactive perforating collagenosistypically occurs in the setting of diabetes mellitus,chronic renal failure, and other pruritic conditions,and this case represents a rare association withdermatomyositis, which may ultimately be helpful inelucidating the pathophysiology of this perforatingdisorder.

Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies. (Less)

Objective.Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature.Methods.Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information.Results.There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining.Conclusion.These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities.