Cutaneous manifestations of COVID-19: a systematic review and analysis of individual patient-level data.

Distinctive patterns in the cutaneous manifestations of COVID-19 have been recently reported. We conducted a systematic review to identify case reports and case series characterizing cutaneous manifestations of confirmed COVID-19. Key demographic and clinical data from each case were extracted and analyzed. The primary outcome measure was risk factor analysis of skin related outcomes for severe COVID-19 disease. Seventy-one case reports and series comprising 144 cases of cutaneous involvement in COVID-19 were included. The most frequently occurring morphologies were: morbilliform (30.6%), varicelliform (18.8%), urticarial (13.2%), chilblains-like (12.5%), and acro-ischemic (9%). The median age of patients was 51 years (mean: 45.9, range: 0 to 91). Patients with chilblains-like eruptions had lower frequencies of extracutaneous COVID-19 symptoms (5/18, 27.8%, P<0.05) and were less likely to have severe COVID-19 disease (2/18, 11%, 95% CI 1.4% to 34.7%, P=0.02). Patients with livedoid and acro-ischemic morphologies had severe COVID-19 more frequently than those with other morphologies (17/21, 81%, 95% CI 58.0% to 94.5%, P<0.0001). The most frequently observed cutaneous manifestations of COVID-19 (morbilliform, varicelliform, and urticarial) are well-described patterns of viral exanthems. However, chilblains-like, livedoid, and acro-ischemic morphologies are not traditionally associated with viral infections and were significantly associated with severity of COVID-19 disease.

Generalized fixed drug eruption to piperacillin/tazobactam and review of literature.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by the development of well-circumscribed, round, dusky erythematous macules and plaques on cutaneous or mucosal surfaces. The reaction occurs on the same mucosal or cutaneous site with subsequent exposures to the offending drug. Although FDE usually manifests as a single lesion, in rare instances, more than one lesion may arise and this is referred to as a generalized eruption. Herein, we present a 31year-old man with history of cystic fibrosis who developed a generalized fixed drug eruption to piperacillin/tazobactam (Zosyn, Pfizer). We discuss our patient's course and review causes and outcomes of generalized fixed drug eruptions in the literature.

Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis.

Lichen planus (LP) is a chronic inflammatory disorder that most often affects middle-aged adults. LP can involve the skin or mucous membranes including the oral, vulvovaginal, esophageal, laryngeal, and conjunctival mucosa. It has different variants based on the morphology of the lesions and the site of involvement. The literature suggests that certain presentations of the disease such as esophageal or ophthalmological involvement are underdiagnosed. The burden of the disease is higher in some variants including hypertrophic LP and erosive oral LP, which may have a more chronic pattern. LP can significantly affect the quality of life of patients as well. Drugs or contact allergens can cause lichenoid reactions as the main differential diagnosis of LP. LP is a T-cell mediated immunologic disease but the responsible antigen remains unidentified. In this paper, we review the history, epidemiology, and clinical subtypes of LP. We also review the histopathologic aspects of the disease, differential diagnoses, immunopathogenesis, and the clinical and genetic correlations.

Treatment of female pattern hair loss.

Female pattern hair loss (FPHL) as a distinctive entity was first described about 30 years ago. The objective of this study was to perform a systematic review of all randomized controlled trials for treatment of FPHL. A preliminary search was carried out in several databases up to August 2008 to identify all randomized controlled trials on nonsurgical interventions for treatment of FPHL. Studies reporting fewer than 10 patients and non-English articles were excluded. Additionally, references of relevant articles and reviews were checked manually in search for additional sources. Among 238 citations found in the preliminary search, 12 fulfilled all criteria to be included in the systematic review. Topical minoxidil 1% to 5% for 24 to 48 weeks was shown to be effective in FPHL and its effect was not related to age or androgen level of patients. In addition, it may be effective in women with FPHL, both with and without hyperandrogenism, and in young and old premenopausal or postmenopausal. In patients with increased serum androgens, oral flutamide but not finasteride or cyproterone acetate was more effective than no treatment. Topical minoxidil is effective in patients with FPHL, with or without hyperandrogenism, but there is limited evidence for the efficacy of antiandrogens.

Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic.

Importance: Beginning in March 2020, case reports and case series linked the COVID-19 pandemic with an increased occurrence of chilblains, but this association has not been evaluated in an epidemiologic study. Objective: To assess whether a correlation exists between COVID-19 incidence and chilblains incidence. Design, Setting, and Participants: A retrospective cohort study was conducted within the Kaiser Permanente Northern California system from January 1, 2016, to December 31, 2020; health plan members of all ages were included. Exposure: COVID-19 incidence in 207 location-months, representing 23 geographic locations in northern California across 9 months. Main Outcome and Measures: Chilblains incidence was the main outcome. The association of chilblains incidence with COVID-19 incidence across the 207 location-months was measured using the Spearman rank correlation coefficient. Results: Of 780 patients with chilblains reported during the pandemic, 464 were female (59.5%); mean (SD) age was 36.8 (21.8) years. COVID-19 incidence was correlated with chilblains incidence at 207 location-months (Spearman coefficient 0.18; P = .01). However, only 17 of 456 (3.7%) patients with chilblains tested during the pandemic were positive for SARS-CoV-2, and only 9 of 456 (2.0%) were positive for SARS-CoV-2 within 6 weeks of the chilblains diagnosis. Test results of 1 of 97 (1.0%) patients were positive for SARS-CoV-2 IgG antibodies. Latinx patients were disproportionately affected by COVID-19 but not by chilblains. Conclusions and Relevance: This cohort study found that in northern California, the incidence of chilblains increased during the pandemic but was correlated weakly with the incidence of COVID-19 across 207 location-months. These findings may have resulted from a causal role of COVID-19, increased care-seeking by patients with chilblains during the pandemic, or changes in behavior during shelter in place.

Unwanted facial hair removal with laser treatment improves quality of life of patients.

BACKGROUND: Unwanted facial hair can have adverse psychological effects on women and reduce their quality of life. OBJECTIVE: To assess the effects of unwanted facial hair removal with laser on improving quality of life. METHODS: In this study, 70 patients treated for unwanted facial hair by laser were assessed by Dermatology Life Quality Index (DLQI) questionnaire on admission and 3 months later after three sessions of laser treatment. RESULTS: The DLQI score before treatment was 9.42 +/- 5.99, which was reduced to 3.12 +/- 3.40 after laser treatment (p <0.05). CONCLUSION: Unwanted facial hair removal with laser can improve the quality of life of patients.

Fox-Fordyce disease exacerbated by hyperhidrosis.

Fox-Fordyce disease is an uncommon disorder primarily affecting postpubertal females. It is characterized by intensely pruritic, papular eruptions in apocrine-gland bearing regions. Rarity and scant literature have resulted in a lack of definitive treatment options or pathognomonic diagnostic indicators. We report a 16-year-old boy with typical findings of Fox-Fordyce disease including numerous, grouped, rounded (1-3 mm), skin-colored papules confined to the axillary and periareolar areas, bilaterally. These lesions started before puberty, and were exacerbated by hyperhidrosis.

A neglected issue in interpretation of results of randomized controlled trials: informative censoring.

The presence of informative censoring is a commonly neglected issue that can lead to inaccurate results in randomized controlled trials. It is mandatory to perform an intention to treat analysis to minimize this source of error.

High-altitude sleep disturbance: results of the Groningen Sleep Quality Questionnaire survey.

OBJECTIVE: To assess the Groningen Sleep Quality Scale (GSQS) for evaluation of high-altitude sleep (HAS) disturbance and employ GSQ questionnaire to describe HAS. METHODS: After the first night's stay at the altitude of 3500 m, quality of sleep for 100 participants (age: 29.13+/-11.01 years; 36 females/64 males) was assessed using the self-administered 15-item GSQS translated into Farsi. RESULTS: Mean GSQS score was 5.36+/-4.32; 38 (38%) participants had a score equal to or less than 2, and 46 (46%) participants had a score equal to or more than 6. A Cronbach's alpha of 0.90 was calculated for internal consistency. Waking up several times during the night was the most prevalent complaint during the first night of sleep, and absolute inability to sleep was the most uncommon problem. CONCLUSIONS: HAS disturbance, which involved many of newcomers to a high altitude, had various harmful effects. For HAS research, GSQS was confirmed to be valid and reliable.

Giant bilateral becker nevus: a rare presentation.

A 14-year-old boy had giant confluent brown patches that were bilaterally distributed on his back, chest, and upper arms, and partially covered by dark coarse hairs. A clinical diagnosis of Becker nevus was made and confirmed histopathologically. We report this patient for the rarity of presentation. Different clinical features of Becker nevi, associated findings, differential diagnoses, and treatment options are discussed.

Corneal stability after discontinued soft contact lens wear.

PURPOSE: To determine the time needed to reach corneal stability after discontinued daily wear of soft contact lenses and to identify corneal topographic and pachymetric changes during this period. METHODS: We prospectively studied the eyes of 21 consecutive soft contact lens wearers evaluated for keratorefractive surgery. Each eye was examined once immediately after lens removal, 3 and 7 days later, and weekly thereafter. At each visit, manifest refraction, keratometry, corneal topography (EyeSys Corneal Analysis system, EyeSys Laboratories, Houston, TX) and pachymetry were performed. Incidence of associated corneal warpage and changes in corneal curvature and thickness during corneal stability time were determined. RESULTS: Of the 42 eyes examined, 26 corneas showed no significant change after the initial evaluation (stable group). The minimum stability time was 3 days in the remaining 16 eyes (unstable group), 7 of which had significant evidence of abnormal topography. Statistical analysis showed no significant differences between two groups regarding age, sex, duration of contact lens wear, and refractive and topographic measures. The mean central corneal thickness on the final visit was significantly different between two groups (P<0.05). CONCLUSION: Contact lens induced corneal warpage may occur in a considerable proportion of soft contact lens wearers. A 2-week contact lens free period seems to be adequate for the cornea to stabilize; however, one cannot predict the minimum time needed for each individual patient. Repeating examinations to document corneal stability before refractive surgery may be a safer alternative.

Respiratory rate within the first hour of ascent predicts subsequent acute mountain sickness severity.

BACKGROUND: Altitude illness results from hypobaric hypoxia at altitudes higher than 2500 meters above sea level. To determine whether vital signs can be used as predictors for severe acute mountain sickness, we carried out a prospective observational study. METHODS: A cohort of 90 individuals (male/female ratio: 2; age: 13 - 65 years) in a mountain hotel's clinic at 3450 meters in Iran were studied from September through October 2006. Demographics and vital signs were measured during the first hour of ascent. The individuals were followed for acute mountain sickness symptoms including headache, dizziness, nausea or vomiting, insomnia, and fatigue. Lake Louise criteria were used to diagnose acute mountain sickness. Severe acute mountain sickness was considered if a score of equal or more than 5 was present. Significance was assigned to values of P<0.05. RESULTS: Acute mountain sickness was diagnosed in 34 (37.8%) participants after 24 hours of ascent. Severe acute mountain sickness was detected in 14 (15.6%) participants. A respiratory rate of 20 or more during the first hour of ascent was recorded for nine (64.3%) patients with severe acute mountain sickness and 15 (19.7%) individuals in the negative/mild acute mountain sickness group. This suggests an association between early high respiratory rates and risk of subsequent severe acute mountain sickness (P=0.001). CONCLUSION: There is an association between a rise in the respiratory rate and susceptibility to acute mountain sickness. This can enable us to predict severe acute mountain sickness and prevent it. Furthermore, Tochal Mountain Hotel guests should be aware of the risk of acute mountain sickness and should be recommended to use prophylactic acetazolamide or dexamethasone before ascent.

Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds.

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63-year-old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)-enriched, high-density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat-killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro-inflammatory interleukin-6 and -8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC-enriched, HDL with topical timolol for the healing of chronic venous leg ulcers. Copyright © 2016 John Wiley & Sons, Ltd.

Ultraviolet Radiation Inhibits Mammary Carcinogenesis in an ER-Negative Murine Model by a Mechanism Independent of Vitamin D3.

Three decades ago, the Garlands postulated that vitamin D3 produced in the skin by ultraviolet radiation (UVR)-induced conversion of 7-dehydrocholesterol to pre-D3 has anticancer effects, thus triggering more than 9,500 publications on D3 and cancer. Here, we report that UVR treatment of transgenic mice of the well-established C3(1)/SV40 Tag mammary cancer model significantly inhibits both autochthonous carcinogenesis and allograft tumor growth, but in contrast neither dietary nor topical D3 influences mammary carcinogenesis in this specific mouse model. Furthermore, UVR's inhibitory effects occur irrespective of whether or not the treatment increases circulating D3 in the mice. The inhibitory effect of UVR on autochthonous tumors occurs at or before the stage of ductal carcinoma in situ. Our studies indicate clearly that UVR can exert D3-independent anticancer effects in C3(1)/SV40 Tag mice. Therefore, supplemental D3 may not mimic all possible beneficial effects of UVR, and uncovering non-D3-mediated mechanisms of UVR tumor inhibition may lead to novel strategies for cancer prevention. Cancer Prev Res; 11(7); 383-92. ©2018 AACR.

Treatment of acute Old World cutaneous leishmaniasis: a systematic review of the randomized controlled trials.

BACKGROUND: Cutaneous leishmaniasis (CL) is caused by different species of Leishmania and transmitted by the bite of infected sand flies. It is a health problem in many countries. OBJECTIVE: This study was performed to assess the evidence for the efficacy of different therapeutic modalities for acute Old World CL, which is usually caused by L major and L tropica. METHODS: Evidence was reviewed according to the hierarchy of evidence. Because there have been no published systematic reviews on this topic to date, the primary source of evidence was individual randomized controlled trials (RCTs). Multiple databases were systematically searched. Using independent double review and published quality review criteria, articles were rated as good, fair, or poor. Treatment benefit data were tabulated, and conclusions were based on the rated strength of published evidence. RESULTS: In all, 50 RCTs met inclusion criteria consisting of 5515 patients in 119 study arms. Reviewed trials were highly variable in quality and methods and generally provide weak evidence for treatment of acute Old World CL. LIMITATIONS: The quality of included studies was generally poor. CONCLUSIONS: Well-designed randomized, double-blind, controlled trials should be designed and conducted to find better evidence for the treatment of acute Old World CL.

Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus.

BACKGROUND: Lichen planus is a common chronic inflammatory mucocutaneous disease, affecting 0.1% to 4% of the general population. There is no published randomized active control clinical trial on pimecrolimus for the treatment of oral lichen planus (OLP). OBJECTIVE: The purpose of this study was to compare the efficacy and safety of pimecrolimus 1% cream with triamcinolone acetonide 0.1% paste in treating OLP. METHODS: In this investigator-blinded parallel-group randomized clinical trial, 40 patients were randomly assigned in two equal groups to receive either pimecrolimus 1% cream or triamcinolone acetonide 0.1% paste 4 times daily for a total of 2 months and followed up for another 2 months. The patients were assessed for painful symptoms measured by visual analog scale, the Oral Health Impact Profile score, and objective clinical score. Nonparametric tests were used to assess the main outcomes. Intention-to-treat analysis was used. RESULTS: Eighteen patients in pimecrolimus group and 17 patients in triamcinolone group finished the 4-month trial course. Both pimecrolimus and triamcinolone groups showed significant improvement in all measured efficacy end points throughout the visits. There was no significant difference between changes from baseline median values of pimecrolimus and triamcinolone groups after treatment termination in terms of visual analog scale score (-9.8 +/- 11.3 vs -8.4 +/- 18.3, P = .70), Oral Health Impact Profile score (-1.5 +/- 2.6 vs -1.6 +/- 2.1, P = .38), and clinical score (-0.7 +/- 0.6 vs -0.8 +/- 0.7, P = .86), respectively. Two patients in pimecrolimus group experienced prominent but transient burning sensation whereas none of the patients in triamcinolone group had any prominent adverse event (P = .24). LIMITATIONS: Blood levels in pimecrolimus group were not measured and carcinogenicity of pimecrolimus, especially in its long-term use for OLP, is yet to be determined. CONCLUSION: This study showed that patients with OLP may benefit from both topical pimecrolimus and triamcinolone acetonide therapy with minimal side effects. Further studies should be conducted to assess the maintenance effects and long-term safety of both drugs (Cochrane skin group identifier: CSG TrialNo. 22).

Think globally, act locally: expert opinions from Asia on the diagnosis and treatment of pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is the most common blistering disease in Iran and many other Asian countries with a relatively high incidence and involvement of both skin and mucous membranes in majority of the patients. AIMS: To assess the opinions of Asian experts on the diagnosis and management of PV. SETTINGS AND DESIGN: It was a questionnaire-based mailed/e-mailed survey. MATERIALS AND METHODS: The questionnaire was sent to 29 dermatologists from different countries of Asia who treat autoimmune blistering disorders, with at least 5 years' experience in this field and who visit at least five new PV patients annually. Questions included duration of experience, number of patients treated and diagnostic and treatment approaches for PV. STATISTICAL ANALYSIS USED: Percentage prevalence; some data are reported as mean +/- SD. RESULTS: All of the 29 physicians participated in the survey; among them, 79.3% visit their patients within 6 months after the onset of symptoms. Diagnosis of PV is confirmed by histologic and direct immunofluorescence examinations by 65.5% of physicians. All of them initiate the treatment with corticosteroids (48.3% with a dose of at least 2 mg/kg/day prednisolone) and 89.7% add adjuvant immunosuppressors at the same time. Of the adjuvant agents used, azathioprine is used by 82.8% of physicians. CONCLUSIONS: Different trends in diagnostic techniques and treatment options for PV among the experienced authorities emphasize the urgent need for large-scale controlled trials in order to reach consensus standards in this field. In addition, regional and worldwide consensus meetings to consider all regional and genetic similarities and differences are highly recommended.

Pigmented Bowen's disease of the finger mimicking malignant melanoma.

Pigmented Bowen's disease is an uncommon in situ squamous cell carcinoma of the skin, which has been rarely reported on the finger. Herein, we report an unusual case of pigmented Bowen's disease of the pulp of the fourth finger in a 20-year-old white woman, which was clinically presented as a superficial, spreading malignant melanoma. Physical examination revealed a solitary hyperpigmented patch, measuring 1 cm in its greatest diameter. The lesion had an irregular, but well-defined margin, and was homogeneously brown with a smooth surface. There was no nodularity or induration in the lesion or in its surrounding skin. A skin biopsy was obtained with the clinical suspicion of malignant melanoma. Histological examination was compatible with the diagnosis of pigmented Bowen's disease. Surgical treatment was then considered and the patient underwent complete excision of the lesion. In spite of its rarity, Bowen's disease should be considered in the differential diagnosis of pigmented lesions, particularly malignant melanoma.

Prehospital hypertonic fluid resuscitation for trauma patients: A systematic review and meta-analysis.

BACKGROUND: Prehospital assessment of a patient's circulation status and appropriate resuscitation with intravenous fluids plays a critical role in patients with obvious hemorrhage or systolic blood pressure below 90 mm Hg. OBJECTIVES: We assessed the efficacy and safety of prehospital administration of crystalloids or colloids to improve the survival rate of trauma patients with acceptable safety profile. DATA SOURCES: We searched SCOPUS, Embase, TRIP database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and PubMed as per search protocol from January 1, 1900 to February 12, 2015. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials were considered. PARTICIPANTS AND INTERVENTIONS: All patients had penetrating or blunt trauma, excluding traumatic brain or thermal injuries. At least one of the comparators should be a crystalloid or colloid. STUDY APPRAISAL AND SYNTHESIS METHODS: Detailed search strategy was developed and utilized. Duplicates were removed from the search results. We, the co-first authors (C.d.C. and F.G.), independently reviewed the article titles and abstracts to assess eligibility. Eligible articles were downloaded for full text review to determine inclusion in the review and analysis. We (C.d.C. and F.G.) performed a methodological quality assessment of each included article. The primary outcome was mortality. The secondary outcomes included adverse events, infections, multiple organ dysfunction score, and length of stay at the hospital. Heterogeneity was measured by I value. An I value greater than 50% was considered to be substantial heterogeneity. Fixed effect analysis and random effect analysis were performed when needed. RESULTS: A total of nine trials (3,490 patients) were included in the systematic review, and six trials were included in meta-analyses. There were no significant differences between hypertonic saline with dextran and lactated Ringer's solution in 1 day using two studies (2.91; 95% CI, 0.58-14.54; p = 0.19) and 28- to 30-day survival rates using another two studies (1.47; 95% CI, 0.30-7.18; p = 0.63). Adding dextran to hypertonic saline did not increase the survival rate (0.94; 95% CI, 0.65-1.34; p = 0.71). Overall, complications were comparable between all groups. LIMITATIONS: The quality of some of the included studies is not optimal. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There is no beneficial effect of hypertonic saline with or without dextran in general traumatic patients. Further trials to evaluate its benefit in patients with penetrating trauma requiring surgery are warranted. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level I.