A systematic review of dermatologic manifestations among adult patients with COVID-19 diagnosis.

BACKGROUND: Infection with COVID-19 is characterized by respiratory, gastrointestinal and neurologic symptoms. However, limited evidence exists of the involvement of the integumentary system among COVID-19 patients and evidence suggests that these symptoms may even be the first presenting sign. OBJECTIVE: To systematically evaluate the literature published on dermatologic signs of COVID-19 in order to educate doctors about the dermatologic signs of COVID-19 infection. METHODS: Lit COVID, World Health Organization COVID-19 database and PubMed were searched using terminology to identify adult patients with confirmed COVID-19 infection and dermatologic manifestations of disease. The last search was completed on 13 July 2020. RESULTS: There were 802 reports found. After exclusion, 20 articles were found with 347 patients with confirmed COVID-19 infection. Within these articles, 27 different skin signs were reported. LIMITATIONS: Limitations of this review include the recency of COVID-19 infection; so, there are limited published reports and that many reports are not by dermatologists, and so, the cutaneous signs may be misdiagnosed or misdescribed. CONCLUSION: Dermatologic manifestations of COVID-19 may be the first presenting sign of infection; so, dermatologists and doctors examining the skin should be aware of the virus's influence on the integumentary system in order to promptly diagnose and treat the infected patients.

Gentian violet for pyoderma gangrenosum: a retrospective chart review.

Pyoderma gangrenosum is a rare autoinflammatory skin disease. Treatment is multifactorial, addressing inflammation, pain, underlying disease, if present, and the wound. Gentian violet has been used for hundreds of years in a variety of dermatologic conditions for its anti-inflammatory properties. This study aims to evaluate gentian violet in wound healing for pyoderma gangrenosum. We conducted a retrospective chart review of patients with pyoderma gangrenosum treated with gentian violet at the Wake Forest School of Medicine Department of Dermatology in the last 10 years. The primary outcome was clinical improvement. Of the 34 cases that met inclusion criteria, 70% improved with gentian violet, 24% had no documented change, 3% initially improved then worsened, and 3% had unclear results. Gentian violet is a safe and cheap treatment that may improve resolution of pyoderma gangrenosum lesions in addition to systemic therapy.

Does daily folic acid supplementation reduce methotrexate efficacy?

Methotrexate is a mainstay treatment for autoimmune and inflammatory conditions in the field of Dermatology. However, in some patients, its use is associated with significant side effects and toxicity. Folate supplementation with either folic acid or folinic acid often mitigates side effects and reduces the incidence of systemic toxicity related to methotrexate. Although the value of methotrexate is clear, debate remains about folate supplementation. There is little agreement about the proper dosing or frequency of folate supplementation as many believe that daily folate supplementation can reduce methotrexate efficacy. Although daily use of folic acid does not appear to affect methotrexate efficacy, dosing of folinic acid close to methotrexate administration may hinder methotrexate efficacy. Therefore, folic acid should be used daily with methotrexate to ameliorate side effects, whereas folinic acid should only be used for methotrexate toxicity.

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.

Erythema elevatum diutinum: a review of presentation and treatment.

Erythema elevatum diutinum (EED) is a rare, chronic and treatable skin condition. It has many histological mimics and is often associated with a variety of underlying systemic diseases, when these are present the management and prognosis dictates the course of the EED. This review aims to highlight the differential diagnosis, clinical manifestations of EED and the possible underlying systemic disease. It is important for clinicians to be aware that EED may predate underlying conditions and the presence of lesions may indicate underlying disease activity. In some cases one may need 'search' for underlying disease. Treatment of these lesions is notoriously difficult. Dapsone is used as the mainstay of treatment, however other options exist. We have highlighted different treatment options and suggested a treatment algorithm. In some cases, treatment may need to be targeted at underlying disease.

Hydroxychloroquine and smoking in patients with cutaneous lupus erythematosus.

Antimalarials, such as chloroquine and hydroxychloroquine, have been used to treat cutaneous and systemic lupus erythematosus for decades with excellent therapeutic efficacy. Smoking seems to inhibit the therapeutic efficacy of antimalarials when treating cutaneous lupus erythematosus (CLE), but the reason behind this observation is unclear. In addition, antimalarials have been associated with several potentially serious adverse effects, including irreversible loss of vision. The aim of this literature review is to discuss the evidence for how cigarette smoking interferes with antimalarial efficacy in the treatment of CLE. Evidence-based data with long-term follow-up will allow determination of the aetiology for diminished antimalarial response, and enable selection of the best treatment to maximize long-term remission in CLE.

Rubeosis faciei diabeticorum: a common, but often unnoticed, clinical manifestation of diabetes mellitus.

In this clinical image, we present the picture of a diabetic patient with rubeosis faciei diabeticorum, a relatively common, but usually unnoticed, microangiopathic complication of diabetes mellitus that could herald other more notorious microangiopathic complications of diabetes mellitus, such as retinopathy. This case will help other physicians to consider rubeosis faciei diabeticorum whenever they face similar cases.

Dramatic verrucae confined to the lower lip.

A 16-year-old boy presented with a 3-year history of development of small papules on his lower lip.

An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed. OBJECTIVE: To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG. METHOD: In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4). RESULTS: By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation. LIMITATIONS: It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown. CONCLUSION: In this pilot study it appears that alefacept treatment may significantly reduce PG severity levels as evidenced by improvement in PGA, Subject Global Assessment, and inflammation scores in all patients. Alefacept may be a safe and effective alternative to current systemic immunosuppressants used to treat PG. Double-blinded, controlled trials are necessary to further evaluate the safety and effectiveness of this treatment.

Development and validation of the Dermatomyositis Skin Severity Index.

BACKGROUND: Dermatomyositis is an autoimmune inflammatory muscle disease with characteristic cutaneous findings of heliotrope eruption, Gottron's papules and a photodistributed eruption with poikiloderma. OBJECTIVES: To develop and validate a tool to assist with objective assessment of the skin disease of dermatomyositis. METHODS: A skin severity index was developed; content validity was evaluated by a panel of experts, and construct validity was assessed by convergence with other measures of disease severity including physician's global assessment of disease, specific skin disease changes (ulceration, poikiloderma and pruritus), and quality of life. Test and retest reliability and interobserver reproducibility were determined. RESULTS: In total, 98 subjects were enrolled. The Dermatomyositis Skin Severity Index (DSSI) showed significant correlation to the physician's global assessment, assessments of poikiloderma and self-assessment of pruritus. Inter-rater reliability showed strong correlations from 0.73 to 1. Test-retest (intrarater reliability) was completed on 33 subjects, and showed correlations above 0.75. The ability of this tool to detect clinical changes with treatment has not been fully evaluated. CONCLUSIONS: The DSSI is a valid and reliable measure of skin disease severity in dermatomyositis and can be used in future clinical trials as an assessment tool.

One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study.

Topical fluorouracil is currently approved for the treatment of actinic keratosis (AK) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions. No randomized, controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial. This prospective, randomized, double-blind, vehicle-controlled study evaluated the effect of pretreatment with 0.5% fluorouracil cream (FC; Carac) or a vehicle cream (VC) once daily for 7 days to the face plus scalp, ears, neck, and/or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery. Efficacy was determined by evaluating AK reduction and clearance (complete lack of AK lesions in the treatment area) at 4 weeks follow-up. Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups. However, the mean number of facial AKs was significantly lower in the FC group at each treatment cycle (p = .011). No serious adverse events were considered related to treatment.

Skin manifestations in vasculitis and erythema nodosum.

Cutaneous lesions are frequent in medium-sized and small vessel systemic vasculitides. The classic cutaneous manifestation of vasculitis is palpable purpura; however the clinical manifestations greatly depend on the size of the vessels affected. They usually do not affect prognosis but relapsing or intractable forms have been described. When skin manifestations are only one of the clinical signs of vasculitis, treatment with corticosteroids and, when indicated, an immunosuppressant, is mandatory, which usually leads to the rapid disappearance of cutaneous lesions. Conversely, when skin lesions are isolated, the diagnosis can be more challenging, but initial treatment may be less aggressive, e.g., dapsone or colchicine, reserving corticosteroids only for those patients in whom the former are ineffective. Erythema nodosum (EN) is the most frequent septal panniculitis. In general it is characterized by the sudden eruption of one or more erythematous and tender nodules or plaques located mainly over the extensor sides of lower extremities. EN resolves with complete "restitutio ad integrum" of the skin in 3-6 weeks. Relapses are uncommon but in patients with idiophatic, streptococcal or EN associated with other upper respiratory tract infections they are more frequent. The main treatment of EN is that of the underlying associated conditions, if demonstrated. Aspirin and other NSAIDs in full doses are often sufficient.

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.

Spontaneously remitting dermatomyositis.

Dermatomyositis (DM) is an inflammatory myopathy of skeletal muscle with characteristic cutaneous findings. It is a rare disorder with a bimodal age distribution that affects almost twice as many women as men. One category of DM, normal-enzyme DM, is characterized by cutaneous changes only at baseline, normal serum muscle enzyme levels and myositis demonstrated by electromyography (EMG) and/or muscle biopsy specimens. Typically, patients with normal-enzyme DM progress to severe muscle involvement and require systemic corticosteroid therapy. The patient we report has normal-enzyme DM confirmed by serial serum enzymes, EMG, and skin and muscle biopsies but is unique in that she never experienced progression of muscle weakness although muscle involvement was documented histologically and by EMG. Follow-up examination after 1 year revealed near-complete resolution of cutaneous involvement after topical therapy and no evidence of muscle weakness.

Pruritus in adult dermatomyositis.

Dermatomyositis has a significant clinical component of pruritus that has not yet been studied. Pruritus can significantly affect the life of patients. The aim of the present work was to study the degree of pruritus experienced by patients. A four-question survey was sent to patients with documented dermatomyositis. The survey used a 100-mm Visual Analogue Scale (VAS) to describe current, worst and daily pruritus, and the effect this has on daily activities. Twenty-six subjects returned completed questionnaires: four had no pruritus; the majority had a significant amount with means above 50 on the VAS. A mean of 44.6 was found for the effect on daily life. Further studies should be performed to examine the prevalence and severity of pruritus in this population and it's effect on their quality of life. Clinicians must be aware of the significant pruritus and provide adequate therapy to improve quality of life.

Topical tacrolimus 0.1% ointment for refractory skin disease in dermatomyositis: a pilot study.

BACKGROUND: Dermatomyositis is an inflammatory disease primarily involving the striated muscles and skin. Muscle disease usually responds to aggressive therapy with systemic corticosteroids. However, cutaneous lesions can be very resistant to systemic and topical therapies, even in combination. More treatment options are needed. Tacrolimus is an immunomodulator now available in a topical ointment. OBJECTIVE: To study the treatment of patients with refractory cutaneous lesions of dermatomyositis using topical tacrolimus 0.1% ointment. METHODS: Six patients with recalcitrant cutaneous lesions of dermatomyositis were included in this brief observational study: five adults and one pediatric patient. Five patients had classic dermatomyositis and one had dermatomyositis sine myositis. RESULTS: All had some degree of improvement of their dermatologic disease following 6-8 weeks of treatment with topical tacrolimus 0.1% ointment. Two had dramatic responses (>90% improvement), one had moderate (40-90%) improvement and three had minimal (20-40%) improvement. CONCLUSIONS: The dermatologic manifestations of dermatomyositis can be very difficult to treat. Multiple systemic and topical therapies have been studied. Combinations of treatments are often used, sometimes still not successfully. The results of this brief observational study using topical tacrolimus ointment for the treatment of refractory cutaneous lesions of dermatomyositis are encouraging. Topical tacrolimus was a useful adjunct in the treatment of the dermatologic component of dermatomyositis in adults and children in this pilot study.

An open-label pilot study to evaluate the safety and efficacy of topically applied tacrolimus ointment for the treatment of hand and/or foot eczema.

BACKGROUND: Hand and foot eczema is a chronic skin disorder. Although topical corticosteroids are often used to control the predominant symptoms of the disease, the chronicity of the condition increases the risk of long-term adverse effects. A safer alternative is needed. OBJECTIVE: To evaluate the safety and efficacy of tacrolimus ointment 0.1% in hand and/or foot eczema. METHODS: Twenty-five adults applied tacrolimus ointment 0.1% to affected areas three times daily for 8 weeks and were followed for 2 additional weeks. RESULTS: Except for vesiculation, compared with baseline there were significant improvements in erythema, scaling, induration, fissuring, composite severity, and pruritus (p<0.007). Two weeks after discontinuing treatment, significant improvement in scaling and composite severity (p<0.03) persisted, whereas erythema, induration, vesiculation, fissuring, and pruritus had returned to pre-treatment levels. CONCLUSION: Tacrolimus ointment 0.1% is a promising corticosteroid alternative for hand/foot eczema.

5-fluorouracil 0.5% cream for multiple actinic or solar keratoses of the face and anterior scalp.

Carac (5-fluorouracil 0.5% cream, Aventis Pharma) was approved by the US FDA in October 2000, for the treatment of multiple actinic or solar keratoses involving the face and anterior scalp. The cream should be applied in a thin film once daily to the skin where actinic keratoses (AKs) are present. When it is applied for 1, 2, or 4 weeks, it is significantly more effective than a vehicle in the management of patients with five or more AKs at pretherapy. Pooled data from the two pivotal trials (n=384) indicate that following 4 weeks of therapy the number of subjects with total AK clearance in the Carac and vehicle groups was 52.9% and 1.6% respectively (p<0.001). Furthermore, the corresponding reduction of AK lesion counts in the Carac and vehicle groups was 82.5% and 19.3%, respectively (p<0.001). Treatment should be continued up to 4 weeks as tolerated by the patient. The most common adverse-effect is facial irritation.

Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial.

BACKGROUND: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. OBJECTIVE: Our purpose was to determine whether docosanol 10% cream (docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. METHODS: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. RESULTS: The median time to healing in the 370 docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients (P =.008; 95% confidence interval [CI]: 2, 22). The docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P =.002; 95% CI: 3, 16.5); (2) complete healing of classic lesions (P =.023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions (P <.001; 95% CI: 8, 25). Aborted episodes were experienced by 40% of the docosanol recipients versus 34% of placebo recipients (P =.109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with docosanol were mild and similar to those with placebo. CONCLUSION: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration.