Andrew G. Franks

Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus

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 anti-double-stranded DNA antibodies.

Raynaud's phenomenon: Pathogenesis and management

Raynauds phenomenon is a common clinical disorder for which patients frequently seek the expertise and care of dermatologists. It is manifested by recurrent vasospasm of the fingers and toes, often associated with exposure to cold temperature or emotional stress. The phenomenon is named after Maurice Raynaud, who, as a medical student, defined the first case in 1862 as episodic, symmetric, acral vasospasm characterized by pallor, cyanosis, suffusion, and a sense of fullness or tautness, which may be painful. Despite more than 140 years of research, the pathophysiology of Raynauds phenomenon continues to elude investigators. Accordingly, although many pharmacologic treatments have been reported, there is still no cure or gold standard therapy. Further, response to treatment varies and is difficult to predict. Recently, there has been renewed interest in finding the pathogenetic mechanisms of Raynauds phenomenon, an effort that has led to more potential targeted therapeutics. The purpose of this review is to discuss recent breakthroughs in the pathogenesis and treatment of Raynauds phenomenon.

Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus

The 1982 ACR classification criteria have become de facto diagnostic criteria for systemic lupus erythematosus (SLE), but a review of the criteria is necessary to include recent diagnostic tests. The criteria were not developed with the help of dermatologists, and assign too much weight to the skin as one expression of a multiorgan disease. Consequently, patients with skin diseases are classified as SLE based mostly on skin symptoms. We discuss specific problems with each dermatologic criterion, but changes must await a new study. We suggest the following guidelines for such a study, aimed at revision of the criteria. 1) The SLE patient group should be recruited in part by dermatologists. 2) The study should evaluate an appropriate international ethnic/racial mix, including late onset SLE as well as pediatric patients. 3) All patients should have current laboratory and clinical evaluations, as suggested in the paper, to assure the criteria can be up-to-date. This includes anti-SS-A and anti-SS-B antibodies and skin biopsies for suspected cutaneous lupus erythematosus except for nonscarring alopecia and oral ulcers. 4) The study should be based on a series of transparent power calculations. 5) The control groups should represent relevant differential diagnoses in numbers large enough to assess diagnostic problems that might be specific to these differential diagnoses. In order to demonstrate specificity of the criteria with a 95% confidence interval between 90 and 100%, each control group of the above should have at least 73 patients.

International consensus for a definition of disease flare in lupus

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: “A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment.” The LFA proposes this definition for lupus flare on the basis of its high face validity.

Resistant discoid lupus erythematosus of palms and soles: Successful treatment with azathioprine

We present the case of two patients with an unusual form of discoid lupus erythematosus that was confined almost exclusively to the palms and soles. In both patients this form of discoid lupus erythematosus did not respond to conventional therapies, which included topical steroids, intralesional steroids, prednisone, quinacrine hydrochloride, hydroxychloroquine sulfate, colchicine, and dapsone. Both patients were then treated with azathioprine. One patient dramatically improved with azathioprine, worsened each time the azathioprine was stopped or reduced, and responded again to the reinstitution of therapy. The other patient began taking azathioprine 8 months ago and has also experienced relief of her symptoms. These cases suggest that discoid lupus erythematosus principally involving the palms and soles is difficult to treat with conventional medication and that azathioprine, which appears to be useful, should be tried after the failure of other therapies.

Anti-C1q antibodies in systemic lupus erythematosus

Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8–4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7–5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2–5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9–6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5–5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3–4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8–38.4, p < 0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Allergic sensitization of the skin and nails to acrylic plastic nails

I RECENT months there has been made available plastic material which can be fashioned into artificial “finger-nails” that are advertised “for those who want long nails.” In addition, the plastic nails may be used by persons who wish to disguise dystrophic or diseased nails or who wish to discourage nail, biting. This plastic material is essentially the same as that used in acrylic dentures, and is marketed as a liquid monomer and powder polymer. The liquid monomer is methyl methacrylate, and the powder is polymethyl methacrylate. One manufacturer claims that the material is completely harmless. However, other manufacturers warn that allergic reactions to this material may be encountered. The acrylic liquid and powder used in artificial “nails” do not require heat for polymerization, but will polymerize and harden at room temperature. These selfcuring acrylic resins are created by inducing polymerization of the mixture of methyl methacrylate monomer and polymethyl methactylate powder with an organic peroxide and an accelerator or promoter. The self-cured resins are not quite as hard as those resins polymerized at high temperature, and they normally contain a somewhat higher residual monomer content than do the heat-cured resins. Nevertheless, these acrylic resins can be fashioned to form excellent plastic nails which remain intact for several weeks. In a previous communication, one of us (A.A.F.) pointed out that methyl methacrylate liquid monomer is a potent sensitizer and can cause allergic contact type of eczematous reactions on the skin and the oral mucosa, When the plastic acrylic “nails” became available, we predicted that allergic reactions to this material would occur. In a short time we were able to observe four cases of allergic eczematous contact reactions of the skin, onychial, and paronychial tissues due to acrylic plastic “nails.” Some of the reactions were rather severe and painful and caused nail changes which lasted for several months. In each case, we were able to prove that it was the liquid monomer that was the sensitizing agent. The powder polymer was inert, allergically speaking.

Skin manifestations of internal disease.

Internal diseases can manifest in a myriad of skin dermatoses ranging from single disorders such as calciphylaxis, cryoglobulinemia, amyopathic dermatomyositis, and Raynaud phenomenon, to spectrum disorders such as the neutrophilic dermatoses and morphea. In this article the underlying causes, triggering events, constitutional symptoms, clinical features and presentations, appearance at various stages, and pathogenesis are described. The course of the diseases and probable healing outcomes are outlined. Finally, examination and diagnostic methods, and therapies and treatments are provided.

Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely due to a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome to that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data supports a role for IL-17 and Th17 cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway.

Successful Treatment of Subacute Lupus Erythematosus With Ustekinumab

A 58-year-old woman presented with a history of subacute cutaneous lupus erythematosus (SCLE) for the past 6 years, associated with photosensitivity, arthralgia, and fatigue. There was no evidence of systemic lupus erythematosus (SLE) or any history of exposure to drugs known to induce SCLE. Previous treatments included hydroxychloroquine sulfate, dapsone, prednisone, azathioprine, mycophenolate mofetil, topical corticosteroids, and tacrolimus 0.1% ointment, with limited benefit. Examination of the skin revealed erythematous and variably hyperkeratotic plaques (Figure, A) covering 70% of the body surface area. Laboratory test results were positive for SS-A/Ro and antinuclear antibodies (titer 1:640) but negative for SS-B/La and double-stranded DNA antibodies. Histopathologic analysis demonstrated vacuolar interface dermatitis, with a superficial and middermal perivascular and periadnexal inflammatory infiltrate consisting of mononuclear cells. There were faint deposits of mucin. Direct immunofluorescence revealed focal cytoid bodies and IgG and fibrin deposits at the dermoepidermal junction. This constellation of findings was consistent with the diagnosis of SCLE. THERAPEUTIC CHALLENGE