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Background: Oncological therapies can cause a variety of mucocutaneous adverse events. Exanthematous adverse events can be challenging in the context of the urgent need for cancer treatment due to their spread, sometimes rapid progression, and mucous membrane or organ involvement., Materials and Methods: This article provides an overview of the most important exanthematic dermatoses as side effects of modern drug-based tumor therapies with diagnostic and therapeutic information for clinicians, taking into account the current literature and guidelines., Results: Exanthematous adverse events of immune checkpoint inhibitors, EGFR antagonists, kinase inhibitors, bispecific T‑cell engagers, and the CCR4 inhibitor mogamulizumab are reviewed in detail., Conclusions: Cutaneous side effects are common across all drug classes and cover a broad spectrum. While some adverse events are specific to one drug class, many exanthemas can occur with both oncological immunotherapies and various targeted therapies. A reliable diagnosis, dose adjustment or discontinuation of the offending agent in consultation with the treating oncologists and appropriate symptomatic therapy are important for correct management. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Delays in the diagnosis and treatment of dermatological conditions in minorities are a well-documented health disparity. We aimed to determine if there was a delay in detection and treatment initiation for dermatomyositis (DM) and amyopathic dermatomyositis (ADM) in patients of different skin tones., Methods: Patients from Montefiore Medical Center who met the criteria for DM and ADM were included in this cohort study. Records were reviewed for date of first documented rash, creatine kinase levels, muscle weakness complaints, and date of first steroid or disease-modifying antirheumatic drug initiation. The median number of days between rash documentation and therapy initiation was compared for patients of different races, including non-Hispanic White, non-Hispanic Black, Hispanic, and other (Asian and unknown). Data were compared in White versus non-White skin., Results: Sixty-three DM and 9 ADM patients met the inclusion criteria. There was a shorter time to treatment initiation in White versus non-White patients, with a median number of 8 days compared with 21 days, respectively ( p = 0.05). Kaplan-Meier curves showed prolonged time to diagnosis and treatment in all other races when compared with White patients ( p = 0.03)., Discussion: It took clinicians longer to diagnose and treat DM and ADM in patients of color. The trends observed emphasize the importance of increasing dermatology education of non-White skin to improve detection and treatment of DM and ADM and minimize health disparities., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The diagnostic approach to febrile skin eruptions in adults requires a systematic methodology, combining an accurate history with careful clinical evaluation. The most frequent etiologies of febrile exanthem in the immunocompetent patient can be categorized as infectious (viral or bacterial) or non-infectious (toxidermia, connectivitis or vasculitis). Mononucleosis, primary HIV infection, secondary syphilis, disseminated gonococcemia and exanthematous drug eruption, are mentioned in detail in this article due to the difficulty of establishing a diagnosis in ambulatory medicine. A clinical vignette is presented to illustrate the reasoning in primary care, with recourse to further investigations depending on the clinical course., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction and Objectives: Lenalidomide is considered a standard of care in multiple myeloma (MM) Some MM patients will develop delayed hypersensitivity to lenalidomide, which can lead to treatment discontinuation. Desensitization to lenalidomide can help these patients to complete treatment courses. Here, we aimed to review lenalidomide-treated MM patients who developed delayed hypersensitivity-induced rash and were treated with desensitization., Methods: A retrospective analysis of medical files of MM patients, who were desensitized to lenalidomide due to delayed hypersensitivity rash. Patients were treated between 2018 and 2022 at Hadassah Medical Center, Jerusalem, Israel., Results: Search of patients yielded 16 patients that underwent desensitization to lenalidomide within the study period. The desensitization protocol consisted of a slow, 3-week-long protocol with lenalidomide's target doses of 10, 15, and 25 mg/day. Of the 16 patients, 10 (62.5%) succeeded to complete the protocol and thus were able to complete lenalidomide treatment cycles. One patient with unsuccessful desensitization was subsequently treated with first-generation IMiD thalidomide, with no rash appearing. None of the patients that were treated with desensitization had severe immune-mediated or non-dermatological adverse reactions., Conclusions: Desensitization to lenalidomide is safe and effective. Discontinuation of lenalidomide in MM patients with delayed hypersensitivity and no contraindication to desensitization should be discouraged. Collaboration between hematologists and allergists is needed., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) are chronic inflammatory skin conditions characterized by eruptions of sterile pustules on the palms and/or soles. Biologic use has been associated with PPP and PPPP development in the literature., Objectives: To identify PPP and PPPP associated with biologics and summarize reported treatments and outcomes., Methods: We systematically searched in MEDLINE and Embase for articles that reported PPP or PPPP during biologic treatment. After a full-text review, 53 studies were included for analysis., Results: We identified 155 patients with PPP/PPPP onset during biologic treatment, with a mean age of 44.1 years and a female preponderance (71.6%). The most frequently reported biologics were adalimumab (43.9%) and infliximab (33.3%). IL-17 inhibitors, secukinumab (7.6%) and brodalumab (1.5%), were reported only in association with PPPP. Overall, 58.8% of patients had complete remission (CR) in 3.6 months and 23.5% had partial remission (PR) in 3.7 months. The most common treatments that led to CR were topical corticosteroids (n = 16) and biologic switching (n = 8)., Conclusions: Clinicians should anticipate PPP or PPPP as potential drug reactions to biologics such as adalimumab and infliximab. Large-scale studies are required to confirm our findings and further explore the pathogenesis for biologic-associated PPP and PPPP., (© 2022 the International Society of Dermatology.)

Background: Adverse drug reactions are frequent, with cutaneous manifestations being the most common. In the hospital environment, the incidence of cutaneous drug reactions varies from 2% to 3%., Objective: To analyze the profile of cutaneous drug reactions, relating clinical forms, suspected medications, histopathological alterations, systemic repercussions, treatment and course., Methods: Clinical, retrospective and observational study of patients seen by the Dermatology Interconsultation team from January 2013 to December 2016., Results: The frequency of cutaneous drug reactions among the evaluated patients was 13.6%, with 219 cases diagnosed. In 65.7%, the reaction was considered mild, of which the most common was exanthema, while in 34.2%, the reaction was considered severe, with DRESS being the main form of reaction(18.2%). Antibiotics (36.5%) and anticonvulsants (10%) were the most involved drugs. In addition to drug discontinuation, systemic corticosteroids were prescribed in 47% of cases and intravenous immunoglobulin (IVIg) in 4.5%. Of the mild forms, in 62%, expectant management and/or exclusive use of symptomatic treatment was used., Study Limitations: Retrospective study, with limitations inherent to this type of investigation; lack of some information in medical records; long evaluation period, with a possible change in external validity., Conclusion: The most frequently identified clinical form was exanthema, and antibiotics and anticonvulsants were the most frequently involved drug classes. About one-third of the patients had severe cutaneous drug reactions, with DRESS being the main one. Cutaneous drug reactions are frequent in clinical practice, and the dermatologist should be called in as soon as possible to assist in the diagnosis and management of these cases., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Introduction: For patients with a rash, the effect of teledermatology workflow on utilization has not been defined. We compared utilization across four teledermatology workflows in patients with a rash., Methods: The observational longitudinal cohort study included 28,857 Kaiser Permanente Northern California members with a new rash diagnosis seen in primary care and with dermatology advice obtained using teledermatology. The workflows differed in camera and image quality; who took the picture; how the image was forwarded; and synchronicity and convenience., Results: On average, 23% of patients had a follow-up office visit in dermatology within 90 days of their primary care visit. In multivariable analysis, the four technologies differed substantially in the likelihood of a follow-up dermatology office visit. In contrast, the likelihood was only negligibly related to medical centre or primary care provider., Discussion: Technologies and workflows that offer the mobility of a smartphone with a high level of synchronicity in communication were associated with standardised co-management of rashes.

Mutations in the interleukin-21 receptor (IL-21R) gene are recently defined as primary immunodeficiency diseases. IL-21R defects result in combined immunodeficiency by affecting the functions of innate and adaptive immune system components.A six-year-old girl was admitted to our hospital with complaints of chronic diarrhea that started after the newborn period and generalized rash over the last three months. She had severe respiratory distress due to Cytomegalovirus (CMV) pneumonia requiring mechanical ventilation and was diagnosed as combined immunodeficiency at another hospital at the age of four. Her physical examination on admission revealed erythematous rash on cheeks, extremities, gluteal region, and lymph node enlargements in cervical, axillary, and inguinal regions. CMV DNA and stool Cryptosporidium parvum were positive. Marginal zone lymphoma -negative for Epstein-Bar virus- was reported in the lymph node biopsy. Targeted next-generation sequencing Ion AmpliSeq™ primary immunodeficiency panel revealed a novel homozygous IL21R c.132delC (p.Ser45fs) mutation.This case is presented to emphasize that IL21R defects should be considered in the differential diagnosis of the patients with recurrent respiratory infections, chronic diarrhea, C. parvum infection, chronic liver disease, sclerosing cholangitis, and malignancy where early hematopoietic stem cell transplantation (HSCT) is life-saving. A total of eight cases with IL21R gene defects have been reported so far. The significance of this case is that it is the first case of malignancy among the published IL-21R deficient patients successfully treated with HSCT.

Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that primarily causes respiratory symptoms. However, an increasing number of cutaneous manifestations associated with this disease have been reported. The aim of this study is to analyze the scientific literature on cutaneous manifestations associated with SARS-CoV-2 by means of a narrative literature review until June 2021. The search was conducted in the following electronic databases: Medline (PubMed), SciELO, and Cochrane Library Plus. The most common cutaneous manifestations in patients with COVID-19 are vesicular eruptions, petechial/purpuric rashes, acral lesions, liveoid lesions, urticarial rash, and maculopapular-erythematous rash. These manifestations may be the first presenting symptoms of SARS-CoV-2 infection, as is the case with acral lesions, vesicular eruptions, and urticaria. In relation to severity, the presence of liveoid lesions may be associated with a more severe course of the disease. Treatment used for dermatological lesions includes therapy with anticoagulants, corticosteroids, and antihistamines. Knowledge of the dermatologic manifestations associated with SARS-CoV-2 contributes to the diagnosis of COVID-19 in patients with skin lesions associated with respiratory symptoms or in asymptomatic patients. In addition, understanding the dermatologic lesions associated with COVID-19 could be useful to establish a personalized care plan.

A 54-year-old woman presented with pruritic rash and hives of 3 days' duration followed by shortness of breath for 1 day. SARS-CoV-2 PCR test for COVID-19 was positive. Cutaneous manifestations of COVID-19 include acral lesions, urticarial rash, erythematous maculopapular rash, vascular rashes and vesicular rash. The cutaneous manifestations are mostly described as self-limiting. Urticarial rashes are not reported as the initial presentation symptom of COVID-19 infection but mostly noted to occur at the same time or after the onset of non-cutaneous symptoms. Management of cutaneous manifestations of COVID-19 affecting quality of life has not been well studied. Antihistamine therapy is the primary recommended therapy. Role of antiviral therapy for severe cases of rash needs to be further assessed., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Skin rash is a common adverse event associated with erlotinib therapy. In severe conditions, the rash could affect patients' QOL. If the rash occurrence can be predicted, erlotinib treatment failures can be prevented. We designed an in vivo study that applied erlotinib regimens resembling its clinical application to evaluate possible erlotinib-induced skin rash biomarkers for humans and simultaneously observe the effects of erlotinib discontinuation, followed with or without dose reduction, on rash development. Rats were divided into four groups: placebo, constant (erlotinib 35 mg/kg on d1-d21), intermittent (erlotinib 70 mg/kg on d1-d7 and d15-d21), and mimic (erlotinib 70 mg/kg on d1-d7 and erlotinib 35 mg/kg on d15-d21). Blood sampling was performed on d1, d8, d15, and d22. The samples were used to measure erlotinib concentrations, the level of hepatic and renal function markers, immune cell percentages, and immune cells' CD45 expression levels. Erlotinib 70 mg/kg generated high mean circulating erlotinib concentrations (>1800 ng/mL) that led to severe rashes. Erlotinib dose reduction following rash occurrence reduced circulating erlotinib concentration and rash severity. After the treatment, the escalation of neutrophil percentages and reduction of neutrophils' CD45 expression levels were observed, which were significantly correlated with the rash occurrence. This study is the first to show that erlotinib-induced skin rash may be affected by the reduction of neutrophils' CD45 expression levels, and this is a valuable finding to elucidate the erlotinib-induced skin rash formation mechanism.

Purpose: To evaluate the natural history and ophthalmologic morbidity of Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and propose a treatment algorithm., Design: Retrospective, interventional case series., Methods: Retrospective chart review of all MIRM patients examined by the department of ophthalmology at a tertiary children's hospital. Diagnosis was established clinically concomitant with either positive Mycoplasma pneumoniae IgM or PCR testing from January 1, 2010, until December 31, 2019. The main outcome measures were best-corrected visual acuity, long-term ocular sequelae, and duration and type of ophthalmic intervention., Results: There were 15 patients (10 male and 5 female) aged 10.9 ± 4.2 years who had primary episodes of MIRM; of those, 4 had multiple episodes. All patients required topical steroid treatment, 3 required amniotic membrane transplantation, and 1 patient underwent placement of a sutureless biologic corneal badage device. There were no patients who suffered visual loss, but 1 was left with mild symblephara near the lateral canthus in each eye and 2 others had scarring of the eyelid margins and blepharitis., Conclusions: The ocular morbidity is significantly less in MIRM than in other closely related syndromes such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. However, these patients still require close observation and a low threshold for intervention to avoid permanent ophthalmic sequelae and possible blindness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

BACKGROUND Coronavirus disease 2019 (COVID-19) infection commonly presents as fever, cough, and shortness of breath in adults. Children are thought to have milder respiratory symptoms and to recover more quickly. We describe a new presentation of COVID-19 infection in children consisting of multisystem inflammation with decreased left ventricular function and evidence of lung disease. CASE REPORT Three children presented with fever, conjunctivitis, dry and cracked lips, rash, and/or cervical lymphadenopathy for at least 5 days. Two of these children required mechanical ventilation, and 1 of the 2 needed extracorporeal membrane oxygenation (ECMO) to support cardiorespiratory function. All of these children had moderate to severe hyponatremia and lymphopenia, which is usually seen in COVID-19. They were treated with intravenous immunoglobulin and high-dose aspirin. All of the children recovered. CONCLUSIONS Early recognition of children with multisystem inflammation is important because they are at increased risk for deterioration. Treatment with intravenous immunoglobulin and aspirin was used because this regimen has been shown to be beneficial in vasculitis of Kawasaki disease. The development of shock due to cardiac involvement may require ECMO.

Introduction:  Total colonic Hirschsprung's disease (TCHD) presents a postoperative challenge due to multiple stools and perineal rash. We propose a protocol developed by pediatric surgeons and ostomy nurses to help prevent and treat hypermotility and severe perineal rash, especially in younger children who are not toilet trained., Materials and Methods:  We retrospectively reviewed our TCHD patients' charts from 2014 to 2017. All patients received a prescribed protocol for the treatment of hypermotility and perineal rash. We describe patients who underwent their pull through before and after the age of urine toilet training, and assessed the number of bowel movements, the perineal skin status, and growth., Results:  We treated 25 patients. Out of 25, 9 patients received a straight ileoanal pull through before the age of 18 months. Nine of 25 patients presented for a second opinion and had redo pull through. The remaining seven presented for bowel management after having a pull through at another institution. All these were treated following the hypermotility protocol. In total, 19 of 25 patients were not toilet trained. The mean number of bowel movements in all groups was 4 (3-5). All had a resolution of perineal rash and liquid stools after 3 months. Eleven of the 25 patients presented with failure to thrive. Two older patients experienced severe proctalgia requiring replacement of the ileostomy., Conclusion:  TCHD patients who underwent definitive pull through had nine high incidence of multiple stool, perineal rash, and low growth. With the implementation of bowel management care to slow the stools and a perineal skin protocol to treat the skin, we believe that these symptoms can be minimized even in patients who are not toilet trained. Since the implementation of this protocol, we have changed our practice to perform the pull through in such patients between the age of 6 and 18 months., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

The asymmetric periflexural exanthema of childhood is an underdiagnosed entity of unknown etiology that affects, most commonly, girls around two years of age. Clinically, it affects only one side of the body and it eventually disappears without the need of any specific treatment. We report two cases of this entity. The first case is a 14-month-old female patient with an erythematosus papular eruption that initiates near the axilla and progresses, in a period of seven days, towards the ipsilateral upper limb and hemithorax, with no other alterations. The second case is a 24-month-old female with a pruriginous erythematosus papular exanthema that begins on the left lower extremity and extends throughout the left hemibody. Due to the characteristics of the exanthema and the age range of the patients, they were diagnosed with asymmetric periflexural exanthema. They both received symptomatic treatment with spontaneous resolution of the condition., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Case Presentation: A 68-year-old man developed an erythematous, papular, pruritic rash on his right thigh 1 month prior to presentation. It subsequently spread to his other extremities and trunk. He also endorsed fevers of > 38.3°C, night sweats, fatigue, shortness of breath, and a dry cough. He was prescribed triamcinolone 0.1% cream for his rash and azithromycin for presumed community-acquired pneumonia, with no improvement in symptoms. He had a history of relapsing polychondritis for which he was prescribed infliximab and low-dose prednisone. He had never smoked tobacco, did not use alcohol or illicit substances, and had no significant travel history., (Published by Elsevier Inc.)

Childhood exanthems are commonly encountered by pediatricians in the hospital and the office. In the last several decades, we have seen a shift in the epidemiology of many of these diseases. After being deemed eliminated at the turn of 21st century, measles has experienced a resurgence secondary to falling vaccination rates, raising public health concerns. A new variant of hand, foot, and mouth disease caused by coxsackievirus A6 has been associated with more widespread and atypical disease, which can present diagnostic challenges to clinicians. Parvovirus B19, which is traditionally associated with fifth disease, is also the leading cause of papular purpuric gloves and socks syndrome, a rare condition with which providers may be unfamiliar. Since the introduction of routine vaccination, there has been a shift in the epidemiology and clinical presentation of primary varicella and herpes zoster. Finally, the recently described phenomenon of Mycoplasma pneumoniae-induced rash and mucositis will be discussed. [Pediatr Ann. 2020;49(3):e116-e123.]., (Copyright 2020, SLACK Incorporated.)

Background: Palmoplantar pustulosis is a chronic inflammatory disease in which sterile, relapsing pustules appear on the palms and soles, possibly in conjunction with other symptoms. The previous Cochrane Review on this topic was published in 2006, before biological treatments were extensively used., Objectives: To assess the effects of interventions for chronic palmoplantar pustulosis to induce and maintain complete remission., Search Methods: We searched the following databases up to March 2019: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of the included studies for further references to relevant randomised controlled trials (RCTs)., Selection Criteria: We considered RCTs including people with palmoplantar pustulosis or chronic palmoplantar pustular psoriasis assessing topical therapy, systemic therapy, combinations of topical or systemic therapies, or non-pharmacological therapies compared with placebo, no intervention, or each other., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our outcomes included 'Proportion of participants cleared or almost cleared', 'Proportion of participants with adverse effects serious or severe enough to cause withdrawal', 'Proportion of participants with at least 50% improvement in disease severity', and 'Proportion of participants with adverse effects'., Main Results: We included 37 studies (1663 participants; mean age 50 years (range 34 to 63); 24% males). These studies reported condition severity differently. Around half of the included trials stated the setting (hospitals, community clinics, or both). More than half of the studies were at high risk of bias in at least one domain. Our included studies assessed mainly systemic treatments (retinoids, ciclosporin, biologics, etretinate + PUVA (combination of psoralens and long-wave ultraviolet radiation) therapy combined, and antibiotics), but also topical treatments (dermocorticoids, vitamin D) and phototherapy (PUVA, ultraviolet A1 (UVA1)). Other interventions were assessed by single studies. The most common comparator was placebo. All results presented in this abstract were assessed in the short term (mean treatment duration was 11 weeks (range 8 to 24 weeks)) and are based on participants with chronic palmoplantar pustulosis. All outcome time point measurements were taken from baseline and assessed at the end of treatment. Short-term and long-term outcomes were defined as measurement up to 24 weeks after randomisation and between 24 and 104 weeks after randomisation, respectively. One trial (188 participants) assessed the topical vitamin D derivative maxacalcitol versus placebo and found that maxacalcitol may be more effective than placebo in achieving clearance (risk ratio (RR) 7.83, 95% confidence interval (CI) 1.85 to 33.12; low-quality evidence), and the risk of adverse effects (such as mild local irritation, pruritus, and haematological or urinary test abnormalities) is probably similar in both groups (RR 0.87, 95% CI 0.64 to 1.19; moderate-quality evidence). Severity was not reported. Two trials (49 participants) assessed PUVA therapy versus placebo or no treatment, providing very low-quality evidence. Adverse effects were reported with oral PUVA (including nausea, ankle swelling, and non-purulent conjunctivitis) and with local PUVA (including blistering, erythema, and pruritus). With regard to the systemic retinoid alitretinoin, one trial (33 participants; moderate-quality evidence) showed that alitretinoin probably makes little or no difference in reducing severity when compared to placebo (RR 0.69, 95% CI 0.36 to 1.30). A similar number of adverse events were reported in both treatment groups, including headache, cheilitis, nausea, arthralgia, and nasopharyngitis (RR 0.84, 95% CI 0.61 to 1.17). Clearance was not reported. There may be little or no difference between etanercept and placebo in achieving clearance (RR 1.64, 95% CI 0.08 to 34.28; 1 study; 15 participants; low-quality evidence); however, the 95% CI was very wide, showing there may be a difference between groups. Severity was not measured. More patients treated with placebo may achieve reduced severity than those treated with ustekinumab, but the wide 95% CI indicates there might be little or no difference between groups and there might be greater effect with ustekinumab (RR 0.48, 95% CI 0.11 to 2.13; 1 study; 33 participants; low-quality evidence). Clearance was not reported. It is uncertain whether guselkumab increases clearance when compared to placebo (2 studies; 154 participants) because the quality of evidence is very low, but guselkumab probably better reduces disease severity (RR 2.88, 95% CI 1.24 to 6.69; 1 study; 49 participants; moderate-quality evidence). Secukinumab is probably superior to placebo in reducing severity (RR 1.55, 95% CI 1.02 to 2.35; 1 study; 157 participants; moderate-quality evidence), but our clearance outcome was not reported. None of these trials reported on occurrence of adverse effects. Only two of the studies discussed above reported adverse effects serious or severe enough to cause withdrawal. Guselkumab may cause more serious adverse events when compared to placebo, but there is uncertainty due to the very wide 95% CI showing there may be little or no difference and showing more events with placebo (RR 2.88, 95% CI 0.32 to 25.80; 1 study; 49 participants; low-quality evidence). Secukinumab probably causes more serious adverse events than placebo (RR 3.29, 95% CI 1.40 to 7.75; 1 study; 157 participants; moderate-quality evidence)., Authors' Conclusions: Evidence is lacking for major chronic palmoplantar pustulosis treatments such as superpotent corticosteroids, phototherapy, acitretin, methotrexate, and ciclosporin. Risk of bias and imprecision limit our confidence. Maxacalcitol may be more effective than placebo in achieving clearance in the short term (low-quality evidence), and the risk of adverse effects is probably similar (moderate-quality evidence). Oral alitretinoin is probably no more effective than placebo in reducing severity, with a similar risk of adverse effects (moderate-quality evidence). Regarding biological treatments, we are uncertain of the effect of etanercept on clearance and the effect of ustekinumab on severity (low-quality evidence). Secukinumab and guselkumab are probably superior to placebo in reducing severity (moderate-quality evidence). Adverse events not requiring withdrawal were not reported for these treatments. Reporting of serious adverse effects was incomplete: compared to placebo, secukinumab probably caused more participant withdrawals (moderate-quality evidence), but we are uncertain of the effect of guselkumab (low-quality evidence). Future trials should assess commonly used treatments using validated severity and quality of life scales., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

A 16-year-old previously well girl presented with bilateral painful lower leg swelling and non-pruritic blanching rash across her torso and upper and lower limbs. These symptoms started after commencing amoxicillin for presumed tonsillitis. She was diagnosed with serum sickness-like illness and started on non-steroidal agents. The rash and painful leg swelling improved over the next 48 hours. However, she subsequently developed fevers, cough and new-onset haemoptysis.She continued to deteriorate with increasing amounts of haemoptysis, work of breathing and escalating respiratory support requirements. Serial chest radiographs showed worsening lung consolidation and enlarging pleural effusion. A CT chest revealed extensive bilateral lung consolidation, most likely pulmonary haemorrhage. Subsequent investigations showed positive classic antineutrophil cytoplasmic antibody, confirming the diagnosis of granulomatosis with polyangiitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Due to the novelty of immune checkpoint inhibitors, their cutaneous adverse events (AEs) have only been recently characterized. This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat cutaneous AEs. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Incidence varies between 35 and 50% for cutaneous AEs among the eight FDA-approved drugs. Although only 2% are reported as grade 3 or 4 events, the impact on quality of life can be significant for these patients and is best described and most severe in ipilimumab trials. Of ipilimumab patients, 43.5% have a cutaneous AE and, at our institution, 20% of them had a dose interruption as a result. This means potentially 9% of patients have dose interruption of ipilimumab because of their cutaneous AEs. In the following chapter, we review the categories of these drugs, common cutaneous effects, their grading, and management options.

Lenalidomide is an immunomodulatory agent that belongs to a family of IMiDs used to treat multiple myeloma. Hypersensitivity and skin reactions are adverse effects of lenalidomide that may lead to discontinuation of its use for multiple myeloma making them contraindicated to other IMiD therapies. Desensitization protocols have been developed to desensitize patients to lenalidomide skin reaction and rash. We report a case series of 5 patients undergoing slow lenalidomide desensitization protocol in an outpatient cancer center setting. Four of the five patients were able to be successfully desensitized to lenalidomide. We also demonstrate safety of using slow lenalidomide desensitization while on combination therapy for control of multiple myeloma.

In view of globalization and the associated transport of goods as well as rising travel activity, imported infections with subtropical and tropical pathogens are increasing in Germany. In returning travelers presenting with fever, general symptoms and skin rash, a number of diseases need to be considered. The clinical appearance of the skin rash, accurate travel history and epidemiological information on country-specific risks are helpful in making the correct diagnosis. In this article we provide an overview of the most common exanthemas in travelers who have returned, associated symptoms, diagnostic methods, therapies, as well as prevention strategies.

Background: Skin rash remains one of the most prevalent and troublesome clinical problems experienced by patients on chemotherapy and targeted therapy. To ensure high-quality care, guidelines are seen as the best guidance. Considering the quality of guidelines varies greatly, a systematical appraisal of the methodological quality of guidelines for the management of skin rash in patients on chemotherapeutic drugs and targeted anticancer therapies was undertaken, in order to identify appropriate ones for healthcare professionals., Methods: A systematic search of databases and Internet was conducted to obtain pertinent guidelines. Two reviewers independently assessed the eligibility of guidelines according to the inclusion criteria. Then the guidelines included were appraised by three researchers with the methodological quality of eligible guideline using Appraisal of Guidelines for Research and Evaluation II (AGREEII)., Results: Totally nineteen guidelines met the inclusion criteria. The quality ranged from good to acceptable in scope and purpose (mean: 78.80%, range: 66.67-94.44%) and clarity of presentation domains (mean: 85.38%, 75.00-91.67%), but not in stakeholder involvement (mean: 50.15%, range: 36.11-75.00%), rigor of development (mean: 23.65%, range: 6.25-70.83%), applicability (mean: 23.96%, range: 4.17-52.08%), and editorial independence domains (mean: 45.18%, range: 0.00-87.50%). Overall, two guidelines were classified as "recommended"., Conclusions: Only two guidelines were recommended to manage skin rash in patients on chemotherapy and targeted therapies, most guidelines issued were of low to moderate quality. Thus, more attention should be paid to the methodological quality of guideline development in this field.

Tropical regions receive a significant part of the traveling population. It is very important that health professionals are familiar with the main tropical skin diseases and able to advice patients appropriately. This article reviews the main tropical diseases of travelers, with an emphasis on diagnosis, management, and prevention. Among others, cutaneous larva migrans, myiasis, tungiasis, Chagas disease, Dengue fever, African trypanosomiasis, filariasis, and leishmaniasis are discussed. Increasing awareness among travelers and health care professionals can help reduce morbidity and mortality. Continued research on new drugs and vaccines is needed to reduce the risks of tropical diseases., (© 2018 Wiley Periodicals, Inc.)

Background: Pregabalin is a medication used to treat epilepsy, neuropathic pain and generalised anxiety disorder. The most common side effects of pregabalin include dizziness, drowsiness, weight gain, ataxia and diplopia. On the other hand, neutropenia and rash are rare side effects of pregabalin, and at the time of writing, there are only two documented cases of neutropenia and one of rash in the literature, none of which involved renal transplant recipients., Case Presentation: We present a 37-year-old renal transplant recipient who was admitted with lethargy, sore throat, urticarial rash and neutropenia after recently being commenced on pregabalin. On physical examination, he had erythematous urticarial rash near his renal transplant scar, on his right elbow, left knee and left wrist. Bacterial/viral serology and immunology were all negative. A blood film confirmed neutropenia and revealed reactive lymphocytes and neutrophil left shift, and those features were compatible with drug reaction. After cessation of the pregabalin, the neutropenia resolved. No other causes of neutropenia or urticarial rash were identified., Conclusion: To the best of our knowledge, we have described the first case of concomitant pregabalin-induced neutropenia and urticarial rash in a kidney transplant patient. This case report highlights the importance of close monitoring when starting any new medications, particularly in the immunosuppressed population, and is relevant because of the growing usage of pregabalin for treating neuropathic pain in such patients and the risk that a missed pregabalin-related neutropenia could lead to unnecessary modifications of the immunosuppressive treatment.

Background: There is increasing recognition of distinct inflammatory eruptions associated with checkpoint inhibitors. A better understanding of their severity, therapeutic response, and impact on cancer treatment is needed., Objective: To analyze the different rashes associated with immunotherapy referred to our institution's oncodermatology clinic and inpatient consultative service and to evaluate their therapeutic response and impact on immunotherapy., Methods: We retrospectively reviewed the medical records of patients referred to the oncodermatology clinic or inpatient dermatology service during 2016-2018 at Yale-New Haven Hospital for eruptions that developed during immunotherapy., Results: In total, 98 patients (51 men, 47 women) treated with checkpoint inhibitors developed 103 inflammatory eruptions, with a range of mean latency of 0.2-17.7 months. A minority of patients (25/103; 24.3%) required immunotherapy interruption; most of these cases involved immunobullous (7/8; 87.5%), lichenoid (8/26; 30.8%), maculopapular (6/18; 33.3%), and Stevens-Johnson syndrome-like (2/2, 100%) reactions. Only 3 of 16 (18.8%) patients who had their immunotherapy interrupted had a grade 2 or 3 flare on rechallenge. Most reactions (93/103; 90.3%) responded to dermatologic therapy or immunotherapy interruption., Limitations: This was a retrospective study from a single tertiary care center., Conclusion: A variety of inflammatory reactions might occur from immunotherapy with differing degrees of severity. While most rashes responded to topical treatment, immunobullous and exfoliative presentations frequently interrupted immunotherapy. Increased awareness and early recognition could reduce the need for unnecessary immunotherapy interruption., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Rash is a common chief complaint for patients presenting to their physician, especially within the pediatric field. The ability to distinguish characteristics of a rash, including morphology, distribution, and configuration, is critical to forming the differential diagnosis. This is the second article of a 2-part review that discusses the common rashes that present in an annular configuration. This articles discuss the presentation, diagnosis, and treatment of fixed drug eruptions, lupus erythematosus, erythema multiforme, urticaria, and erythema migrans. Although this review is not inclusive of all conditions that present with annular lesions, it can serve as a starting point for physicians managing a patient with these complaints. [Pediatr Ann. 2019;48(3):e135-e138.]., (Copyright 2019, SLACK Incorporated.)

There is a broad differential diagnosis for the presentation of fever and maculopapular rash in an adult. Although some causative conditions are benign, others are medical emergencies that require prompt diagnosis. We describe various conditions that result in a fever and maculopapular rash in adults. These include infectious processes (meningococcemia, infectious mononucleosis, West Nile virus, zika virus, rubella, primary human immunodeficiency virus, parvovirus B19, ebolavirus), tick-borne illnesses (Rocky Mountain spotted fever, ehrlichiosis), and hypersensitivity reactions (exanthematous drug reactions). We also provide an algorithm to aid in the diagnosis of the patient with fever and maculopapular rash. Such conditions that can occur in adults but are seen predominantly in children are discussed in the article "Rash with maculopapules and fever in children" of this issue., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Several medical conditions can cause children to present with fever and a maculopapular rash Although some presentations are benign, others may be medical emergencies, which warrant a prompt diagnosis. We review some of the more common causes of fever and maculopapular dermatitirs, rash including infectious processes (roseola; rubeola; rubella; parvovirus B19; hand, foot, and mouth disease; scarlet fever; meningococcemia; Epstein-Barr virus infection), hypersensitivity reactions (exanthematous drug reactions), and vasculitis syndromes (Kawasaki disease). We have included a diagnostic algorithm to facilitate rapid identification of the etiology of the rash and fever. Those conditions that can occur in children but are seen predominantly in adults are discussed in the contribution "Rash with maculopapules and fever in adults" in this issue., (Copyright © 2018. Published by Elsevier Inc.)

Adverse reactions to drugs are not frequent in childhood. Cutaneous reactions are the most frequent in this age group. Mild cutaneous reactions are immediate or delayed adverse reactions that do not seriously compromise the clinical condition of children. The patients usually early improve and recover the state of health. Although it is difficult to define the prevalence accurately, we could affirm that the rate adverse reaction to drugs are often over estimated by both the families and the physicians. Therefore, children may be prone to loss of school days and inappropriate or sub-optimal treatments. However, the identification of a true adverse reaction to drugs allows adequate treatment and alert to further exposure to harmful drugs.

Objective: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice., Methods: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis., Results: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05)., Conclusion: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Skin eruptions are commonly encountered in the neonatal and infant period and can be a source of concern for providers and parents alike. We present a brief, clinically focused discussion on topics commonly encountered by the pediatrician with a focus on pearls of knowledge to help distinguish diseases from one another and from more serious conditions. We review miliaria, transient neonatal pustular melanosis, neonatal cephalic pustulosis, erythema toxicum neonatorum, diaper dermatitis, seborrheic dermatitis, and atopic dermatitis. Treatment strategies are also discussed. [Pediatr Ann. 2019;48(1):e16-e22.]., (Copyright 2019, SLACK Incorporated.)

Introduction : Multiple three drug combination regimens have been approved for the treatment of multiple myeloma in the last few years. Triplets have become the new standard of care for transplant eligible and ineligible patients with newly diagnosed as well as relapsed multiple myeloma. Novel agents have a unique profile of side effects. The management of toxicities is important to maintain quality of life and maximize treatment duration and benefit. Areas covered : This article reviews efficacy data, incidence of key adverse events and provide recommendations and expert opinion regarding how to manage common toxicities in triplet therapies. Relevant publications and abstracts were searched in PubMed, ASH, ASCO and EHA meetings. Guidelines from IMWG, NCCN, ESMO and ASCO, published trial protocols and prescribing information were used to formulate recommendations for the management of toxicities. Expert commentary : Side effects are a critical factor guiding the selection of optimal chemotherapy regimens for multiple myeloma. The majority of toxicities encountered with triplet therapies are reversible and can be readily managed with supportive care and dose modifications.

This explorative and qualitative study, based on 27 interviews during two months of fieldwork, describes pese, an affliction of the skin that has conspicuously stayed under the radar of medico-anthropological research in Kigoma, a rural city in the northwest Tanzania. The condition reminds of a locally better known condition labeled kisigo, raising the question why two concepts of the same affliction exist side by side. It seems indicative that the two illness concepts stem from different cultures and that each specializes in an explanatory model: the former witchcraft (sorcery) and the latter spirit possession. Moreover, a symbiotic relation seems to exist between the healing traditions of the Bembe and the Ha. Government policies prohibiting witchcraft and targeting traditional healers seem to have created a situation where witchcraft practices and beliefs have come to represent the periphery and survive there, clandestinely.