Maculopapular Exanthema Research Articles

Dermatological manifestations among patients with COVID-19: The Sri Lankan experience

Background: Patients diagnosed with COVID-19 demonstrate a wide spectrum of cutaneous manifestations, some of which are at a high prevalence. These manifestations, of which some are unique, have been considered to occur due to COVID-19 infection and the associated inflammatory response. Furthermore, there are reports on exacerbation of previously diagnosed dermatoses and cutaneous side effects of medications and vaccines administered.Methodology: The first phase of the study included a descriptive cross-sectional study conducted at the National Hospital of Sri Lanka (NHSL) among PCR-positive COVID patients to identify their skin conditions. Secondly, to ascertain an overall understanding of the country’s situation, a comprehensive questionnaire was circulated among the members of the Sri Lanka College of Dermatologists, to obtain information on the patients they have encountered.Results: Out of the patients at NHSL only 1.7% (n=8) had developed associated skin manifestations. Two (0.4%) developed novel conditions: thrombophlebitis and a maculopapular exanthem. Six (1.3%) patients had exacerbation of pre-existing conditions including eczema, psoriasis and discoid lupus erythematosus. The dermatologists revealed a wide variety of manifestations with the majority experiencing an exacerbation of pre-existing conditions and a few developing novel lesions including COVID-toes and Kawasaki-like diseases in children which are considered specific for COVID-19.Conclusions: The study demonstrates a range of COVID-19-associated dermatoses. These can present before or with other COVID-19 symptoms. Further, studies are necessary to precisely determine the timing and pathophysiology of different manifestations. Dermatological findings are important and should prompt the early involvement of dermatologists as appropriate.

Les toxidermies au service de Dermatologie-MST du CHU de Conakry (Guinée): responsabilité des antirétroviraux

Background: Antiretroviral (ARV)-induced toxidermia is increasingly reported. They most often complicate ARV therapy and can compromise the therapeutic future of patients living with HIV. The aim of this study was to determine the frequency of ARV-induced toxidermia, to identify the ARVs responsible, to describe the clinical forms encountered and the evolutionary modalities of patients. Material and methods: This was a cross-sectional study from January 2000 to December 2018. The study consisted in identifying and documenting all cases of ARV-induced toxidermia during the study period at the Dermatology-IST department of the University Hospital of Conakry. Internationally accepted diagnostic criteria were used for diagnosis. Accountability was based on the Begaud criteria. Results: We recorded 47/198 (23.7%) cases of ARV-induced toxidermia during the period. The mean age of the patients was 35.02± 1.60 with extremes of 23 and 61 years. The sex ratio was 0.7. The toxidermia encountered were Stevens-Johnson syndrome (SJS) in 22/47 (46.8%) cases, toxic épidermal necrolysis (TEN) in 8/47 (17%) cases, overlap syndrome between SJS and TEN in 1/47 (2.1%) cases, maculo-papular exanthema in 10/47 (21.3%) cases, urticaria in 4/47 (8.5%) cases and erythema pigmentum fixans in 2/47 (4.3%). The ARVs involved were nevirapine in 44/47 (93.6%) cases and efavirenz in 3/47 (6.4%) cases. We recorded 8/44 (17%) deaths. Conclusion: The occurrence of toxidermia during antiretroviral therapy is a major challenge. Therefore, ARVs with a high risk of toxidermia should be removed from the ARV regimens offered to patients.

Tools to improve the diagnosis and management of T-cell mediated adverse drug reactions.

Delayed drug T-cell immune-mediated hypersensitivity reactions have a large clinical heterogeneity varying from mild maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin necrosis and blistering as seen in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Given the knowledge gaps related to the immunopathogenesis of these conditions, the absence of validated diagnostic tools and the significant associated morbidity and mortality, patients with SCARs often have limited drug choices. We performed a comprehensive review aiming to evaluate in vivo diagnostic tools such as delayed intradermal skin and patch testing and ex vivo/in vitro research assays such as the lymphocyte transformation test (LTT) and the enzyme-linked ImmunoSpot (ELISpot) assay. We searched through PubMed using the terms “drug allergy,” “in vivo” and “ex vivo” for original papers in the last 10 years. A detailed meticulous approach adapted to the various clinical phenotypes is recommended for the diagnostic and management of delayed drug hypersensitivity reactions. This review highlights the current diagnostic tools for the delayed drug hypersensitivity phenotypes.

Toxicoderma in a child as a complication after a bedbug bite

Background. Toxic dermatitis is an adverse skin reaction caused by various factors. Analysis of clinical cases helps identify problems, and plan future studies, which can change the understanding of the consequences of the disease. The purpose was to improve the diagnosis of allergic dermatoses in children, to analyze clinical and paraclinical features of their course, and biomarkers of sensitization to allergens. Materials and methods. Presentation of a case study was a basis for discussion, as well as literature search in the MEDLINE and Scopus databases. The study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the ethics committee of the institution mentioned in the work. Informed consent of child’s parents was obtained for the research. Results. The clinical picture of toxic dermatitis is very diverse, almost any type of lesion can occur, and often the clinical symptoms are very similar to skin diseases that are not caused by various toxic agents. The most common clinical symptom is maculopapular exanthema. Conclusions. The peculiarity of the presented case is toxicoderma in a child after a bedbug bite. It is important to establish the correct diagnosis of toxic dermatitis, identify toxic agent, stop its exposure and treat the adverse reaction, usually with antihistamines and corticosteroids.

Association of HLA Alleles with Antiepileptic Drug-Induced Mild Cutaneous Reactions: A Case-Control Study of a Northeast Han Chinese Population.

Human leukocyte antigen (HLA) is associated with drug-induced cutaneous adverse reactions, including antiepileptic drugs (AEDs). HLA gene polymorphism has a regional discrepancy, and it is therefore important to study it in different populations. To investigate the role of HLA in AED-induced mild cutaneous adverse drug reactions (cADRs) in a Northeast Han Chinese population. A case-control study was performed in the First Hospital of Jilin University between August 2016 and March 2017. In total, 26 patients with mild cADRs induced by AEDs and 23 AED-tolerant control patients were included. Sequence-based typing (SBT) was used to detect HLA-A and HLA-B genotypes. Differences in genotype frequencies between groups were assessed using Fisher's exact test. In the mild cADRs group, 22 patients (84.6%) presented with maculopapular exanthema (MPE) and four patients (15.4%) presented with an isolated itch. The median duration between the AED exposure and cADRs was 7.5 days (IQR, 3 - 14 days). We failed to find statistically significant differences in HLA alleles between the cADRs group and the control group when considering all the drugs included in our study together or when considering oxcarbazepine (OXC), carbamazepine (CBZ), and levetiracetam (LEV) alone (P > 0.05). Our findings indicated that there was no correlation between HLA alleles and AED-induced mild cADRs in the Northeast Han Chinese population.

Distinct Characteristics and Chronology of Amoxicillin-Associated Reactions in Pediatric Acute Care Settings

Amoxicillin-associated reactions (AARs) in children presenting as rashes are common, and recent data suggest that >90% tolerate amoxicillin on re-exposure. However, additional data would help pediatricians and allergists gain confidence in referring and testing children who experienced systemic symptoms perceived as "worrisome," thus leading to urgent medical evaluations. By characterizing the entire spectrum of AAR symptoms in pediatric patients presenting to emergency department (ED)/urgent care (UC) settings, we sought to increase our diagnostic acumen to guide subsequent allergy evaluations. To fully characterize clinical features of rash and systemic symptoms in children presenting to the ED/UC with AARs. A retrospective chart review of children seen in the ED/UC from July 1, 2015, to June 30, 2017, was conducted. Clinical features, chronology, and seasonality were detailed, and cases were classified into 3 previously described AAR phenotypes: maculopapular exanthem (MPE), urticaria, and serum sickness-like reactions (SSLRs), if they experienced joint symptoms. Children (n= 668; median age: 1.8 years) presented to the ED/UC with urticaria (44%), MPE (36%), and SSLRs (11%) typically on days 7 to 10 of amoxicillin. Although children with SSLRs were more frequently treated with corticosteroids (28%, P < .0001) and exhibited higher rates of "worrisome" features (fever, angioedema, or gastrointestinal symptoms; 73%, P < .0001), delayed-onset systemic symptoms were identified frequently in all 3 groups. ED/UC reutilization was unexpectedly high with 66 children (10%) returning to the ED/UC for re-evaluation. "Worrisome" symptoms are common in children presenting to the ED/UC with AARs. Future studies are needed to determine the impact on subsequent referral and allergy testing.

159 Diagnostic overlap of drug-induced acute interstitial nephritis with cutaneous involvement and drug-induced hypersensitivity syndrome

A common clinical dilemma is distinguishing maculopapular exanthem (MPE) with systemic symptoms from severe cutaneous drug reactions, such as drug-induced hypersensitivity syndrome (DIHS). Drug-induced acute interstitial nephritis (DI-AIN) with MPE can be especially challenging to differentiate from DIHS with renal involvement. It is crucial to distinguish DI-AIN from DIHS as the prognosis and treatment differ. Our goal was to estimate the percentage of published DI-AIN cases meeting RegiSCAR criteria for DIHS and characterize the outcomes.

Exanthema after lamotrigine use: A clinical case

Introduction: Lamotrigine is a phenyltriazine compound that inhibits sodium and potassium channels in presynaptic neurons. Maculopapular exanthema is a common side effect of Lamotrigine therapy, occurring most frequently during the first eight weeks of treatment in approximately 3–10% of patients. Case Report: A 74-year-old female had started Lamotrigine 50 mg due to emotional lability and depression. About 8–9 weeks after the introduction of the drug she presented a rash with exanthema, maculopapular in appearance. The attending physician suggested discontinuation of the medication and reevaluation. Complete regression of the clinical picture occurred. No severe skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis were observed. Conclusion: Lamotrigine is effective for a variety of types of conditions involving neuronal excitability, however, such drug exposes the individual to side reactions ranging from mild skin rashes to even those leading to hospitalization. Measures such as adherence to the manufacturer’s dosing guidelines, titration, and intrinsic characteristics of the individual can minimize this effect.

Drug-Induced vs. Viral Maculopapular Exanthem-Resolving the Dilemma.

Maculopapular exanthem is a commonly encountered presentation in routine clinical practice, and differentiation between its two most common etiologies, i.e., viral- and drug-induced, often poses a diagnostic dilemma. Clinical, hematological and biochemical investigations are seldom reliable in distinguishing between a drug reaction and a viral exanthem. Certain key histopathological features such as the presence of a moderate degree of spongiosis, extensive basal cell damage with multiple necrotic keratinocytes and dermal infiltrate rich in eosinophils or lymphocytes and histiocytes may favor a drug exanthem, while distinctive epidermal cytopathic changes and lymphocytic vasculitis point towards a viral etiology. Similarly, notable immunohistochemical markers such as IL-5, eotaxin and FAS ligand may support a diagnosis of a drug-induced maculopapular eruption. Histopathological and immunohistochemical evaluations may help in distinguishing between the two etiologies when faced with a clinical overlap, especially in patients on multiple essential drugs when drug withdrawal and rechallenge is not feasible.

Delayed cutaneous adverse drug reactions to sympathomimetics after oral intake of over-the-counter medications

Sympathomimetics are a therapeutic class of drugs wich aim is to mimic adrenaline and noradrenaline, contained in many over-the-counter medications such as “Humex Cold”. To date, 32 cases of delayed hypersensitivity induced by pseudoephedrine have been reported in the literature ranging from MPE to severe cutaneous adverse drug reactions, including 3 PEAG and 4 EMP. Cross-reactivities within sympathomimetics are not yet well established. We describe here two case reports of delayed cutaneous drug reactions to sympathomimetics, one maculo-papular exanthema and one acute generalized exanthematic pustulosis. We evaluated cross-reactivity and review the sympathomimetic drugs to be able to make a summary table. We first did patch tests with the molecule that caused the initial skin reaction. Then, searching for cross-reaction: we tested with patch tests thirteen sumpathomimetics with different properties. We also performed skin biopsies on positive patch tests for histological analysis in RNA later for the patient who presented acute generalized exanthematic pustulosis. Patient who did maculopapular exanthema had a negative patch test to pseudoephedrine after two series of allergological tests but did a recurrence of maculo-papular exanthema after oral provocation to pseudoephedrine and with an emergency treatment with ephedrine. A new allergological workup revealed a positive ephedrine patch test at 72 h. The search for cross-reactivity had highlighted during a 3rd exploration positive patch tests at 72 h for: ephedrine, pseudoephedrine in three different molecules (Humex, Actifed, Rhinadvil) anda positive patch test to phenylephrine. Patient who did an acute generalized exanthematic pustulosis had a positive pseudephedrine patch test. No cross-reactivity with other sympathomimetics was found. Literature is weak regarding cases of delayed cross-hypersensitivity to sympathomimetics even if searching for cross-allergies seems to be necessary. We propose summary table and a list of of sympathomimetic drug to test when faced to a delayed cutaneous drug reaction.

Bosutinib-Induced Stevens-Johnson Syndrome and Evidence of Tolerance to a Structurally Dissimilar Tyrosine Kinase Inhibitor

Bosutinib is a breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitor (TKI) used for the treatment of chronic myeloid leukemia (CML). Patients on TKIs may develop severe cutaneous adverse reactions (SCARs). A 73-year-old female with CML treated with a second-generation TKI (bosutinib) was evaluated after developing fever and a maculopapular exanthema with skin-peeling affecting her lips, oral mucosa, and genitals 10 days after starting the medication. She required hospitalization, bosutinib discontinuation, and management with intravenous corticosteroids and antibiotics. Patch testing was contraindicated due to the severity of the reaction. The patient was subsequently challenged with first-generation TKI along with careful observation without any adverse reactions. She has not reported any adverse reactions while on therapy in the last two years. In patients who have suffered from SCARs, the suspected triggers must be avoided in all instances. In some cases, the underlying condition limits the use of alternative agents, but low-concentration patch testing may help guide alternative therapies within the same medication group. There appears to be a low cross-reactivity among generational TKIs, and our patient benefited from treatment with a structurally dissimilar alternative TKI for her CML.

Skin tests in the work-up of cutaneous adverse drug reactions: A review and update.

Skin tests, including patch tests (PTs), prick tests, and intradermal tests (IDTs), are useful in identifying the culprits of cutaneous adverse drug reactions (CADRs), and determining safer, alternative drugs. PTs have a low sensitivity but are valuable in investigating maculopapular exanthema (MPE), as well as severe CADR, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and in particular, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). To ensure their specificity, at least 10 control tests should be performed. Prick tests are mainly used in the evaluation of immediate-type hypersensitivity and can be performed with all drugs, except opiates. IDTs can be used to explore immediate and delayed-type hypersensitivity, if an injectable form of the drug exists. Except for SJS/TEN, IDTs should be performed by injecting 0.02 mL of the drug. We here provide a practical, up-to-date review on the use of these skin tests in the work-up of CADRs. Numerous negative controls for drug PTs, as well as criteria for the immediate and delayed positivity of prick tests and IDT, are included. It should be emphasized that a negative result never excludes the potential responsibility of a drug in a CADR.

The Activation Pattern of Drug-Reacting T Cells Has an Impact on the Clinical Picture of Hypersensitivity Reactions.

Rationaleβ-lactam antibiotics cause drug hypersensitivity reactions (DHR) with various clinical pictures from minor affections like maculopapular exanthema (MPE) and urticaria to severe cutaneous adverse reactions and anaphylaxis. Currently, two different reactivity patterns have been shown to initiate an immune reaction by activating T cells—the hapten concept and the pharmacological interaction with immune receptor (p–i) concept.ObjectivesIn this study, the relationship between the reactivity pattern of drug-reacting T cells of drug allergic patients and their clinical picture has been investigated.FindingsDrug-reacting T-cell clones (TCCs) were isolated from patients hypersensitive to β-lactams. Analysis of their reactivity pattern revealed an exclusive use of the hapten mechanism for patients with immediate reactions and for patients of MPE. In patients suffering from drug reactions with eosinophils and systemic symptoms, a severe DHR, analysis of isolated drug-reacting TCC identified the p–i concept as the unique mechanism for T-cell activation.ConclusionsThe results show a shift from hapten pattern in mild allergic reactions to p–i pattern in severe life-threatening allergic reactions. They strongly argue against the current preclinical risk evaluation of new drugs based on the ability to form haptens.

Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies.

Background:Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported.Patients and Method:We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated.Results:A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1–16 days). RDD was performed using a protocol involving 8–13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6–6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment.Conclusions:RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

Oral Challenge without Penicillin Skin Tests in Children with Suspected Beta-Lactam Hypersensitivity

AbstractObjective A misdiagnosed “penicillin allergy” is a common problem in childhood. Recently, skipping skin tests (STs) and performing a direct oral challenge test (OCT) have become an increasingly common approach in children with suspected β-lactam (BL) allergy. In our study, we aimed to evaluate the safety and efficacy of OCT without using ST in children who had a history of hypersensitivity reactions with BL antibiotics.Materials and Methods We retrospectively evaluated direct OCT outcomes in children with both nonimmediate and immediate-type reaction history with BL antibiotics. STs were not performed before the challenge test. The patients were monitored for 4 hours after the challenge and continued using the drug in two divided doses for 3 days at home.Results In this study, 72 patients were included, with median age of 7 years (interquartile range: 4; min: 1 year to max: 16 years), and of these, 56% were male. Forty-five subjects (63%) reported immediate-type adverse reactions. The most common clinical manifestation was urticaria/angioedema (51%, n: 37) and maculopapular exanthema in 46% (n: 33) of patients, respectively. The most commonly suspected drug was 71% amoxicillin-clavulanate. A 3-day OCT without preceding ST was performed in all patients. Only three patients (4.2%) showed a positive response to the oral drug challenge test. None of these reactions observed was more severe than index reactions.Conclusion Performing OCT without STs is a safe and convenient method to exclude BL hypersensitivity in the pediatric age group.

Завозные случаи лихорадки денге у жителей Республики Татарстан

The article presents an analysis of clinical-epidemiological and laboratory-instrumental data of 15 patients with dengue fever (DF), residents of the Republic of Tatarstan, who visited regions endemic for DF as tourists. To verify the diagnosis, PCR diagnostics of blood serum for dengue virus RNA and determination of dengue virus serotypes were carried out. The classical form of the disease of moderate severity was diagnosed in 14 (93.3%) patients. The clinical picture was characterized by an acute onset, fever, chills, myalgia, arthralgia. The total duration of the febrile period varied from 3 to 7 (4.1 (2.09)) days. In 7 (46.7%) patients, maculopapular exanthema of various localization was observed, in 43% it was hemorrhagic in nature and was accompanied by itching (28.6%). In 5 (33.3%) cases, dyspeptic syndrome developed. 4 (26.7%) patients were diagnosed with respiratory syndrome. Hematological changes were characterized by thrombocytopenia in 93.3% (105.6 (35.9) 109/l) and leukopenia in 86.7% (3.2 (1.9) 109/l) of patients. 7 (46.7%) patients had a moderate cytolytic syndrome with a predominance of ALT (61 (43.3) U/l) and AST (59.6 (36.9) U/l) activity in the early period of the disease. In 7 (46.7%) patients, an increase in the pulmonary pattern of both lungs with perivascular and peribronchial changes was diagnosed radiographically. Sonographic examination of the abdominal organs revealed an increase in the size of the liver and spleen in 3 (20%) patients. Thus, imported cases of DF in the Republic of Tatarstan were characterized by the development of the classical moderate form caused by serotypes 1-3. Due to the increased DF incidence in the Russian Federation and, in particular, in the Republic of Tatarstan, it is necessary to improve medical alertness in diagnosing the disease characterized by fever combined with arthralgia, myalgia and exanthema in people who returned from endemic countries. Due to the lack of vaccination in the Russian Federation, it is necessary to inform patients who recovered from DF about the risk of developing a hemorrhagic form of the disease in case of re-infection.

Development of a real-time RT-PCR assay for the detection of pan-human parechoviruses

BackgroundParechoviruses (PeV-As), which constitute a new genus within the family Picornaviridae, have been associated with numerous localized outbreaks of serious diseases, such as coryza, pneumonia, maculopapular exanthem, and conjunctivitis. However, to the best of our knowledge, only a few laboratories worldwide conduct tests for the identification of this group of viruses. Therefore, in this study, we aimed to develop and validate a real-time RT-PCR assay for the identification of PeV-As.MethodsTo design and validate a real-time PCR primer–probe targeting the 5′-UTR region of PeV-As, the 5′-UTR sequences of PeV-As available in GenBank were aligned using the MUSCLE algorithm in MEGA v7.0. Thereafter, the highly conserved 5′-UTR region was selected, and its primer–probe sequence was designed using Primer Premier v5.0. This primer–probe sequence was then evaluated for specificity, sensitivity, and repeatability, and for its validation, it was tested using fecal samples from 728 healthy children living in Beijing (China).ResultsThe PeV-A real-time RT-PCR assay detected only the RNA-positive standards of PeV-A genotypes (1–8, 14, 17, and 18), whereas 72 serotypes of non-PeV-A EV viruses were undetected. In addition, the VP1 region of these 11 PeV-A genotypes that tested positive were amplified using the primers designed in this study. Typing results indicated that eight, one, and two strains of the 11 were PeV-A1, PeV-A4, and PeV-A6, respectively. We also determined and presented the genetic characterization and phylogenetic analyses results corresponding to these 11 VP1 region sequences. Furthermore, real-time RT-PCR assay showed good sensitivity with LOD of 102 copies/μL. Positive results in eight parallel experiments at each concentration gradient from 107 copies/μL to 102 copies/μL, indicating good repeatability.ConclusionOur findings suggested that the real-time RT-PCR assay developed in this study can be applied for routine PeV-A identification. We detected PeV-A1, 4 and 6 genotypes in the 728 faecal samples using this method. Additionally, we believe that our results will serve as a foundation for further studies on PeV-As and facilitate the expansion of the gene sequence information available in GenBank.

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine.

Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.

Dermatological Manifestations of COVID-19 in Patients Reporting to a Tertiary Care Hospital in Rawalpindi, Pakistan.

IntroductionThe clinicopathological description of dermatological manifestations of COVID-19 leaves much to be desired. There is a need to determine their association with disease severity, outcome, and other clinical variables.ObjectivesThe objectives of this study are to record and histopathologically examine the cutaneous manifestations of COVID-19 and correlate these to age, disease severity, and mortality.MethodsAll confirmed COVID-19 patients admitted to a single tertiary healthcare hospital in Rawalpindi, Pakistan, were included. Their diseases were classified as mild, moderate, severe, and critical. The recent onset skin eruptions in these patients were recorded via photographs along with relevant clinical data. The photographs were independently reviewed by a group of three dermatologists without knowledge of the clinical information. The skin manifestations were divided into disease-specific and nonspecific categories using an already defined algorithm. Histopathological examination of skin manifestations was conducted.ResultsA total of 23% (n=47) had “new” skin manifestations. Specific skin findings were seen in 21.6% (n=44), which consisted of ecchymosis/purpura in 50% (n=22), maculopapular exanthem in 18% (n=8), livedo reticularis in 16.2% (n=7), ischemia/gangrene in 16.2% (n=7), perniosis in 15.9 % (n=7), vesiculo-bullous rash in 9% (n=4) and urticaria in 4% (n=1). Non-specific findings were seen in 6% (n=13) and included bedsores, dermatitis passivata, dryness, herpes labialis, oral ulcerations, and nasogastric tube-induced ulcerations. There was a significant association (p=0.03) between disease severity and specific skin lesions. Ischemia/gangrene was significantly associated with COVID-19 disease severity and mortality. Vesiculobullous lesions were associated with higher mortality, though not with disease severity. Livedo reticularis had a higher-than-expected count in critical disease, albeit statistically insignificant. The association of maculopapular exanthem and ecchymosis/purpura with severe/critical disease was statistically insignificant. Urticaria was significantly associated with low disease severity. Mean age with specific manifestations was 56.86 ± 15.81 and with nonspecific/without any manifestations was 42.58 ± 16.96, a highly significant difference, with p-value < 0.001. Old age (>60 years) was significantly associated with ecchymosis (p=0.038), maculopapular exanthem (p=0.021), and vesiculo-bullous rash (p=0.029). Histopathology varied according to the type of skin lesion.ConclusionsDermatological manifestations coexist in many patients and tend to appear more in severe cases of COVID-19 among the older age group and only minimally in mild/moderate cases. Their presence could help set prognostic criteria of COVID-19 disease in the future.

Tre-P-23 - Papuloerythroderma of Ofuji successfully treated with oral retinoids

Papuloerythroderma of Ofuji (PEO) is a rare skin disorder, which affects predominantly older males with male to female ratio 4:1. It is characterized by pruritic erythematous papules, which might progress to erythroderma. Exanthema typically spares the skin folds (deck-chair sign). Common laboratory findings include lymphopenia, peripheral eosinophilia and elevated serum IgE. Histological image generally shows non-specific inflammatory reaction and needs to be correlated with clinical and laboratory findings. PEO has been associated with cutaneous T-cell lymphomas (CTCL). However, this relationship remains poorly understood. Diagnosis of PEO should be established by exclusion and PEO individuals should be closely monitored for possible onset of CTCL. Case 1: A 85-year-old man with a 2-year history of pruritic non-confluent erythematous papules sparing the skin folds. Lymphopenia, eosinophilia and elevated serum IgE. Histology shows edematous changes of papillary dermis with mixed inflammatory infiltrate comprising multiple mast cells, eosinophils as well as isolated plasma cells. The diagnosis of PEO was made based on the typical clinical, laboratory and histopathological features. Case 2: A 95-year-old man with a 3-month history of pruritic maculopapular exanthema. Indolent multiple myeloma has been diagnosed 4 years prior to rash onset. Histology shows a non-specific spongiotic dermatitis with multiple eosinophils. In this context, eosinophilia found in the laboratory work-up allows to establish probable diagnosis of PEO. Pathogenesis of PEO is poorly elucidated and development of effective treatment guidelines thus remains challenging. As skin-homing Th2/Th22 cells seem to play a role in the pathogenesis of PEO, use of dupilumab, monoclonal antibody against IL-4Rα, has recently been investigated. We report a successful resolution in two patients with PEO using combination therapy of oral retinoids (acitretin, 10 mg/d) and local treatment (topical corticosteroids, tacrolimus, polidocanol). Our findings correlate well with recent reports suggesting higher success rates of oral retinoids compared to PUVA therapy or oral corticosteroids, yet with a more favourable safety profile and patient tolerance. Papuloerythroderma of Ofuji (PEO) is a rare skin disorder, which affects predominantly older males with male to female ratio 4:1. It is characterized by pruritic erythematous papules, which might progress to erythroderma. Exanthema typically spares the skin folds (deck-chair sign). Common laboratory findings include lymphopenia, peripheral eosinophilia and elevated serum IgE. Histological image generally shows non-specific inflammatory reaction and needs to be correlated with clinical and laboratory findings. PEO has been associated with cutaneous T-cell lymphomas (CTCL). However, this relationship remains poorly understood. Diagnosis of PEO should be established by exclusion and PEO individuals should be closely monitored for possible onset of CTCL. A 85-year-old man with a 2-year history of pruritic non-confluent erythematous papules sparing the skin folds. Lymphopenia, eosinophilia and elevated serum IgE. Histology shows edematous changes of papillary dermis with mixed inflammatory infiltrate comprising multiple mast cells, eosinophils as well as isolated plasma cells. The diagnosis of PEO was made based on the typical clinical, laboratory and histopathological features. A 95-year-old man with a 3-month history of pruritic maculopapular exanthema. Indolent multiple myeloma has been diagnosed 4 years prior to rash onset. Histology shows a non-specific spongiotic dermatitis with multiple eosinophils. In this context, eosinophilia found in the laboratory work-up allows to establish probable diagnosis of PEO. Pathogenesis of PEO is poorly elucidated and development of effective treatment guidelines thus remains challenging. As skin-homing Th2/Th22 cells seem to play a role in the pathogenesis of PEO, use of dupilumab, monoclonal antibody against IL-4Rα, has recently been investigated. We report a successful resolution in two patients with PEO using combination therapy of oral retinoids (acitretin, 10 mg/d) and local treatment (topical corticosteroids, tacrolimus, polidocanol). Our findings correlate well with recent reports suggesting higher success rates of oral retinoids compared to PUVA therapy or oral corticosteroids, yet with a more favourable safety profile and patient tolerance.