Maculopapular Eruption Research Articles

Clinical and Histopathological Features and Potential Pathological Mechanisms of Skin Lesions in COVID-19: Review of the Literature.

In recent weeks, several reports have emerged of skin lesions with different clinical presentations in COVID-19 cases. All dermatologists should be aware of these cutaneous lesions, which may be early clinical symptoms of infection. We reviewed the literature on cutaneous manifestations in the PubMed database from December 2019 and June 2020. From the cases described as case reports or series in 57 recent articles, it appears that skin lesions (i) are highly varied, (ii) may not be related to the severity of the condition and (iii) resolve spontaneously in a few days. The frequency of these lesions in COVID-19 patients varies between 1.8% and 20.4%. The major clinical forms described were maculopapular eruptions, acral areas of erythema with vesicles or pustules (pseudochilblain), urticarial lesions, other vesicular eruptions and livedo or necrosis. The lesions were mainly localized in the trunk and extremities. The majority of patients were male, aged between 4.5 and 89 years. A minority of the patients were children presenting with acral, chilblain-like lesions, papulo-vesicular eruptions or Kawasaki disease-like pediatric inflammatory multisystem syndrome. The mean duration of the lesions was a few days, but some lasting as little as 20 min and others as long as four weeks have been reported. The mean latency time in the majority of cases was between 1 and 14 days; however, in some patients, lesions appeared 2 to 5 days before the onset of COVID-19 symptoms. The histopathological features of these lesions also vary, corresponding to the diversity of clinical manifestations. These features underline the nature of epidermal and dermal vascular lesions—and in severe cases, microvascular injury and thrombosis—associated with COVID-19, and provide important clues to their pathological mechanisms.

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases.

SummaryBackgroundThe cutaneous manifestations of COVID‐19 disease are poorly characterized.ObjectivesTo describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings.MethodsWe carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis.ResultsThe lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. The severity of COVID‐19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular).ConclusionsWe provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID‐19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID‐19, using a consensus method to define morphological patterns associated with COVID‐19.We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition. Linked Editorial: Hay et al. Br J Dermatol 2020; 183:3–4.

Association between HLA genotype and antiseizure medications (ASMs)-induced maculopapular eruption among epilepsy patients in Xinjiang, China

PurposeTo determine genetic associations between antiseizure medications (ASMs)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in Xinjiang, China. MethodsA total of 409 patients were enrolled in this study, including 36 subjects with ASMs-induced MPE (case group) and 373 ASMs-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 409 Uighur patients using next-generation sequencing (NGS). The carried rate of HLA alleles were compared between the case group, the control group, and the general Chinese population. ResultsThe carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with both the ASMs-tolerant group (p = 0.000, odds ratio (OR) = 23.92, 95 % confidence interval (CI) = 3.96–74.84; p = 0.000, OR = 21.40, 95 % CI = 3.55–67.52; p = 0.030, OR = 4.69, 95 % CI = 0.90–61.73 and p = 0.000, OR = 18.94, 95 % CI = 3.15–60.58; respectively), and the general Chinese population (p = 0.000, OR = 21.34, 95 % CI = 3.31–38.98; p = 0.000, OR = 23.92, 95 % CI = 3.96–74.84; p = 0.019, OR = 5.53, 95 % CI = 0.14–19.86 and p = 0.000, OR = 21.67, 95 % CI = 3.68–11.73; respectively). Moreover, the carried rate of the HLA-B*4001 allele was significantly higher in the ASMs-tolerant group when compared with the ASMs-MPE group (p = 0.024, OR = 5.13, 95 % CI = 1.01–9.99). ConclusionsIn this study, we identified for the first time that the carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with the ASMs-tolerant group.

P0328DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) SYNDROME: THE GREAT MIMICKER SECONDARY TO LENALIDOMIDE IN PERITONEAL DIALYSIS

Abstract Background and Aims DRESS syndrome is a rare, idiosyncratic, potentially life-threatening adverse drug reaction, characterized by latent period after intake of the inciting drug (2-6 weeks), fever higher than 38.5°C, skin eruptions (usually pruritic maculopapular rash or diffuse erythematous eruption), eosinophilia (in 66-95% of patients), mononucleosis-like atypical lymphocytes (27-67% of pts), thrombocytopenia, lymphadenopathy (in 54% of pts) and multiple organ involvement. In 50-60% of patients, two or more organs are involved, most frequently liver (hepatomegaly, hepatitis with ALT> 2 times and ALP> 1,5 times the upper limit), kidney (acute interstitial nephritis, most often induced by allopurinol) and lung (interstitial pneumonia). Cardiovascular involvement occurs lately (up to four months after recovery) with myocarditis, decreased LV function and elevated troponin. Different mechanisms have been involved in the pathogenesis of DRESS syndrome, including detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation and reactivation of human herpes, including Epstein-Barr virus and HHV-6. Cacoub et al reported 172 cases of DRESS: the most frequently reported “trigger-drugs” were carbamazepine, allopurinol, sulfasalazine, phenobarbital, nevirapine and HHV-6 infections were positive in 80% of cases. Interestingly, the culprit drug could be able to trigger viral reactivation, inducing a pathogenic anti-viral CD8+ response. According to available literature, the drug should be withdrawn and, in cases of visceral involvement, systemic steroids are indicated (1 mg/kg orally with slow taper over 3-6 months). In severe cases, other therapies include IVIG, plasmapheresis and immunosuppressant drugs. CASE REPORT A 72-year-old male, affected by ESKD in peritoneal dialysis and hypokinetic heart disease, started lenalidomide for multiple myeloma with bone involvement. After 18 days he presented a violet maculopapular rash involving >50% of his body, fever (38,5 °C), leukopenia with CRP <0,8 mg/dl. Lenalidomide was withdrawn and started oral steroid, anti-histamine and levofloxacin. One week later he was admitted for a syncopal episode. Laboratory tests revealed leukocytosis (12.250/mm), eosinophilia (until 56%, 4.550/mm) and cholestatic-cellular liver damage (ALT 1448 U/l, ALP 308 U/l) requiring albumin infusion. Extensive infectious and autoimmune workup was negative, including ANA test, immunological liver diseases tests, blood cultures, viral/bacterial tests, except for HHV6 reactivation (420 copies/ml). US abdominal study was negative, while DLCO test showed an important diffusive deficit. ECHO showed a reduced LV ejection. Skin biopsy demonstrated sparse vacuolization of epidermis and dermal-epidermal inflammation with some eosinophils and CD8+ T cells, suggesting a drug reaction. For clinic and laboratory features RegiSCAR score system and Japanese consensus group categorized this case as “definite DRESS” respectively with score 6 and 7. So we started IVIG (1 gr/Kg for 2 days) and prednisone with reduced dose for comorbidities (0,8 mg/Kg daily, tapered to 0,6 mg/Kg after 1 week); the patient gradually improved but after 1 week, DRESS syndrome relapsed with rash, elevated GOT and GPT and troponin until 330 ng/l with normal ECG; he has just started steroid bolus and IVIG. Conclusion The variety of drugs, the clinical course with slow resolution and relapse and HHV-6 reactivation suggest that drugs cannot be the sole etiology of DRESS. Precise mechanism of lenalidomide in DRESS syndrome is not clear and its immunomodulatory activity could contribute in the hypersensivity reaction. Only few cases are reported in literature, but with the increasing use of lenalidomide a broad workup and a careful approach are important for a fast diagnosis

Valproic acid-induced DRESS confirmed by positive patch test

Introduction Valproic acid (VPA) is one of first-line traditional antiseizure drugs used for a variety of clinical conditions. Antiepileptic drugs most frequently associated with DRESS are phenytoin, phenobarbital, and carbamazepine. Methods Here, we present a case of DRESS induced by valproic acid and confirmed by patch test. Results A 55-year-old man was treated with ceftriaxone, vancomycine and valproate for brain abscess. Three weeks later, the patient suffered from erythematous maculopapular eruptions without mucous membrane involving a large area of his face, back, bilateral shoulders and both lower limbs. Laboratory investigations revealed leukocytosis (15,6 × 109/L) with atypical lymphocytosis, elevated levels of transaminases and gamma-glutamyl transpeptidase. Viral serology including hepatitis B and C, cytomegalovirus, Epstein–Barr virus, parvovirus B19 and human herpes virus 6 were negative. In our case, definitive features of DRESS were present (score of 6 on RegiSCAR). DRESS-induced by valproic acid was suspected, antieepileptic drug was withdrawawn and corticosteroid therapy was initiated. Patch tests for valproic acid performed 4 months after complete recovery induced a strongly positive skin reaction in 48 and 72 hours. Discussion It is well known that aromatic antiepileptic drugs such as carbamazepine, phenobarbital and phyentoine are common causative drugs of DRESS syndrome. However, only a small number of case reports have described valproic acid-induced DRESS syndrome. Aromatic antiepileptic drugs may induce DRESS in patients with a defect in the epoxide hydrolase in patients with a history of reaction to the drug. The diagnosis of valproic acid-induced DRESS may be difficult. Therefore, Patch testing can be helpful in confirming the imputability. Conclusion Clinicians should be aware of the possibility of DRESS with valproic acid. The rule out of other possible diagnoses should not delay the interruption of the suspected drug and the beginning of supportive therapies.

The Association Between HLA-A*03:01 and HLA-B*07:02 Alleles and Oxcarbazepine-induced Maculopapular Eruption in the Uighur Chinese Population

PurposeTo determine genetic associations between oxcarbazepine (OXC)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in the Uighur Chinese population. MethodsA total of 208 patients were enrolled in this study, including 20 subjects with OXC-induced MPE (case group) and 188 OXC-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 208 Uighur patients using next-generation sequencing (NGS). ResultsThe carried rate of HLA-A*03:01 was significantly different between the OXC-induced MPE group and the tolerant group (7/20, 35% versus 4/188, 2.13%; P = 0.000, odds ratio [OR] = 24.77, 95% confidence interval [CI] = 6.41–95.65). Additionally, the carried rate of HLA-B*07:02 was significantly different between the OXC-induced MPE group and the tolerant group (3/20, 15% versus 2/188, 0.011%; P = 0.000, odds ratio [OR] = 16.41, 95% confidence interval (CI) = 2.56–105.09). ConclusionsHLA-A*03:01 and HLA-B*07:02 may be the risk alleles for MPE in the Uighur Chinese population.

Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): A prospective study from China and Italy

Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): A prospective study from China and Italy

Tinidazole: Another Therapeutic Option for Syphilis?

After the incidental observation of an almost complete resolution of maculopapular eruption in a patient having simultaneously secondary syphilis and trichomonas vaginalis infection, we extended the treatment with tinidazole (500 mg 4 times daily for 7 days) to 10 other early syphilis patients before the start of the conventional penicillin treatment. All patients showed marked improvement of their lesions in a few days. After the introduction of the conventional penicillin regimen, the lesions further improved and VDRL titers declined at least 4-fold within 6 months in all patients. Tinidazole is a 5-nitroimidazole derivative as well as metronidazole but with a longer plasma half-life. It is activated intracellularly by bacterial/parasitic enzymes to a redox cytotoxic intermediate that damages large protein molecules and inhibits repair and transcription of DNA affecting also the cell wall. With this action, tinidazole might also have a synergic action with penicillin and doxycycline, facilitating the entry of such drugs. It is possible that tinidazole has the same bactericidal action on spirochetes other than Borrelia, such as Treponema pallidum, explaining its rapid therapeutic action on the lesions of early syphilis. Whether this action could be confirmed by studies on larger series of patients, tinidazole might be considered in case of allergy to penicillin or other antibiotics usually prescribed in syphilis.

Skin Test for Cutaneous Adverse Drug Reactions

Background: The incidence of drug eruptions is increasing during the last few years due to a large number of new medications. Early detection of the causative agent and the prevention from exposure are crucial managements in terms of drug eruption, mainly to prevent its recurrence. Objective: To understand skin test as a diagnostic modality in drug eruption, which includes skin patch test, skin prick test, and intradermal test. Literature review: Drug eruption is a form of skin eruption triggered by the use of medications, topical or systemic, in the right dose and indication. The manifestation can vary from maculopapular, urticaria, pustular, and bullous eruption; from the most nonsignificant to a life-threatening reaction. A diagnostic procedure is critical to discover the type of drugs that cause the eruption, i.e., skin test, specific IgE measurement, histamine-release test, and provocation test. Skin test is the first choice in the diagnostic process as it is simple, easy, practical and has high sensitivity and specificity. Conclusion: Skin test is one of the many available diagnostic tools. However, both false positive and false negative results might still arise. The experts are currently attempting to come up with more accurate and practical tests to aid the diagnostic of drug eruption, thus preventing its occurrence.

Hypersensitivity reactions to proton-pump inhibitors: Clinical presentation, diagnosis, and management.

Background: Proton-pump inhibitors (PPI) are one of the most commonly prescribed drugs, and they are generally well tolerated. However, several immediate and delayed hypersensitivity reactions due to PPIs have been reported. Objective: To review the clinical characteristics and management of immune-mediated immediate and delayed hypersensitivity reactions to PPIs. Methods: We performed a search of a medical literature data base from January 1980 to October 2019 by using keywords that included "proton-pump inhibitors" and "hypersensitivity." Results: Anaphylaxis is the most-common clinical presentation in patients with immediate hypersensitivity reactions to PPIs, followed by urticaria and/or angioedema. Occupational contact dermatitis, maculopapular eruption, fixed drug eruption, symmetrical drug-related intertriginous and flexural exanthema, and severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have also been reported with PPIs. Conclusion: The current knowledge and severity of the reported reactions indicated the importance of consideration of a causal relationship between hypersensitivity reactions and PPIs, and awareness of the existence of cross-reactivity among PPIs.

Skin manifestation and diagnosis of febrile diseases by COVID-19 and other ribonucleic acid viruses: The diagnostic clues

Many febrile diseases caused by ribonucleic acid virus infection demonstrate cutaneous manifestations with preceding prodromes. This review provides a flowchart highlighting the diagnostic clues of viral exanthem. Besides febrile prodromes, patients with chikungunya virus have severe arthralgias and macular hyperpigmentation on the noses. Coronavirus disease 2019 demonstrates unique acrocyanosis and pseudofrostbite besides erythematous rash and urticaria, suggesting abnormal coagulation. Dengue fever should be suspected when patients in the tropical region present with biphasic fever, headache, retroorbital pain, and centrifugal morbilliform rash. Dengue hemorrhagic fever, a potentially fatal complication, results from systemic vascular leakage. High-temperature fever and sudden-onset severe headache raise the possibility of Ebola virus infection. Patients with hand-foot-and-mouth disease may experience morbilliform or vesicular eruption, especially over the hands, feet, and oral mucosa. In acute human immunodeficiency virus infection, maculopapular eruptions often appear on the face and neck after prodromes. Primary human T-lymphotropic-III virus infection can induce widespread maculopapular or roseola-like exanthem, sparing the hands and feet. Cutaneous manifestations of rotavirus include generalized maculopapular rash, Sweet's syndrome, Henoch–Schonlein purpura, Gianotti–Crosti syndrome, and acute hemorrhagic edema. Rubella is usually suspected when low-grade fever and lymphadenopathy are accompanied by a discrete pinpoint-sized maculopapular rash, which spreads and diminishes faster than measles. Cough, coryza, and conjunctivitis followed by morbilliform eruptions and Koplik's spots are diagnostic of measles. Exanthem of Zika virus comprised of small pruritic papules that extend downwards. Laboratory testing is helpful in making a definitive diagnosis. Viral isolation, measurement of immunoglobulin M (IgM) or IgG, and/or reverse transcription polymerase chain reaction are useful diagnostic tools with favorable sensitivity and specificity.

Acute generalised exanthematous pustulosis caused by anti-malarial drug: a case report

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous reaction that usually occurs after drug intake. Antimalarials like hydroxychloroquine have long been incriminated in the literature. This is a case of AGEP occurring after the consumption of an antimalarial other than hydroxychloroquine; labeled as Synriam® (piperaquine and arterolane). A 35-year-old Cameroonian woman presented to our outpatient unit for the sudden onset of generalized maculopapular and pustulous pruritic skin eruption, associated with fever (39.5°C). The eruption had started 4 days after the consumption of arterolane and piperaquine drug combination. The patient been living with Takayasu disease and chronic renal failure for 5 years. She had neutrophilia at 10 000/ul, a hypereosinophilia at 1500/ul, and raised markers of inflammation with and transaminitis. This clinical picture was suggestive of AGEP. The treatment consisted of applying sterile Vaseline and betamethasone 0.05% cream with an antiseptic bath every day. AGEP is a rare but severe cutaneous drug reaction with a female preponderance. The time from drug intake to onset of symptoms and varies from hours to days. The diagnosis is established when a set of clinical, laboratory and histological arguments are available. The management is relatively simple and prevention consists of withdrawing the causal agent. AGEP is a severe cutaneous reaction that can occur after drug intake. Cases of AGEP secondary to antimalarial drug intake other than hydroxychloroquine have not yet been described.

Scarlatiniform eruption-a rare extrahepatic manifestation of acute hepatitis A infection

A 12-year-old girl presented with a one-week history of fever associated with jaundice, vomiting and skin rash on the fifth day of illness. She denied any abdominal pain, diarrhoea, history of recent shell-fish or traditional medication ingestion. On examination, she appeared jaundice, and there was sandpaper-like rash on the trunk and extremities (A). Laboratory investigations revealed severe transaminitis (AST 849 U/L, ALT of 1092 U/L) and predominantly direct hyperbilirubinaemia. Hepatitis A IgM was reactive whereas leptospirosis, hepatitis B and C serology were non-reactive. The antistreptolysin O titre and throat swab culture were negative. Ultrasound of the hepatobiliary system demonstrated normal liver parenchyma without sonographic evidence of biliary obstruction. She was admitted for intravenous fluid and symptomatic therapy. She remained well with improving transaminitis, and did not exhibit any signs of liver failure. She was discharged after 5 days of hospital stay. The rash disappeared and liver function test normalized during a followup review 2 weeks post-discharge. Many types of skin rashes can occur as a part of the serum sickness-like prodrome of acute viral hepatitis which is thought to be due to immune complex deposition. An evanescent rash was reported to be present in 14% of patients with acute hepatitis A. Cutaneous vasculitis associated with hepatitis A can appear as an erythematous maculopapular eruption affecting the buttocks and lower extremities. Scarlatiniform rash has not been reported previously in hepatitis A infection. Clinicians should be alert to this rare extrahepatic manifestation of hepatitis A infection when encountering patients with skin rash and severe transaminitis.

IADVL Position Statement and Recommendations on Post Lockdown Dermatology Practice Amidst the Covid -19 Pandemic (IADVL Academy and IADVL Executive Committee).

IADVL Position Statement and Recommendations on Post Lockdown Dermatology Practice Amidst the Covid -19 Pandemic (IADVL Academy and IADVL Executive Committee).

Epoetin-alfa induced pruritic maculopapular eruption: Case report and literature review.

Erythropoiesis-stimulating agents (ESA) are commonly used in clinical practice to improve anaemia. Despite a number of patients successfully treated without adverse events, the complications have been previously reported. To report and review the characteristics and management of ESA hypersensitivities. Case reports and related articles associated with ESA use, published between January 1999 and December 2018, were retrieved through Electronic databases (MEDLINE® and PubMed®). Forty-seven ESA patients with various immediate and delayed hypersensitivity reactions caused by epoetin and pharmaceutical excipients were identified from nineteen studies and one case report in this paper. Fatal hypersensitivity to ESA and ESA-allergic cross-reactivities have been documented. Desensitization or change of EPO molecular structure has been reported as successful methods of re-introducing the drug. ESA hypersensitivity in the various allergic reactions and cross-reactivity have been documented. Desensitization and Epoetin structural changes could be successful methods to re-introduce the drug.

Confusion in determination of two types of cutaneous adverse reactions to drugs, maculopapular eruption and erythema multiforme, among the experts: A proposal of standardized terminology.

The clinical classification of cutaneous adverse reactions by drugs should be clearly distinguished to avoid conceptual confusion and inconsistency. Although dermatologists appear to have established a roughly common consensus for cutaneous adverse reactions, some types are more rigorously defined than other, possibly misleading classifications. To assess the consensus on the clinical classifications, we investigated the concordance rate of diagnosis by Japanese experts through a snap visual inspection of various clinical pictures exhibiting erythema multiforme and maculopapular eruption types of cutaneous adverse reactions. The experts were shown images on a screen and were then asked to decide whether to classify cases as maculopapular eruption or erythema multiforme type, and the concordance rates were calculated. Overall, the mean concordance rate was 71.6% (standard deviation, 17.3%), and only 33.8% of cases had a 90% or more concordance rate. Our study shows that the determinations of erythema multiforme and maculopapular eruption types by the existing classification criteria were confusing even among experts, which prompted us to standardize the terminology. We propose clinically defining erythema multiforme type as generalized macules mainly of 1cm or more with a tendency of elevation and coalescence, and maculopapular eruption type as generalized erythema other than erythema multiforme type. Currently, the clinical definitions of cutaneous adverse reactions are poorly described, which may be problematic upon analyzing large volumes of data. Our proposal for a new terminology will enhance the accuracy and consistency of information for the correct analysis of cutaneous adverse reactions.

Drug eruptions associated with tumor therapy: Great imitators

Many studies have investigated cutaneous reactions to antitumor drugs and found them to be quite numerous. We describe drug eruptions that may be associated with different therapies by class: antimetabolite chemotherapeutics, genotoxic agents, spindle inhibitors, signal transduction inhibitors, and immunotherapies. Methotrexate is most often associated with mucocutaneous reactions, alkylating antimetabolite agents with hyperpigmentation, and platinum antimetabolite agents with type I IgE-mediated hypersensitivity reactions. Anthracycline derivatives can induce the hand-foot syndrome in patients, and bleomycin is associated with a bleomycin-induced flagellate erythema. Taxane spindle inhibitors can result in acneiform eruptions, which may also be seen with use of epidermal growth factor receptor inhibitors. Imatinib and its derivatives can cause a truncal maculopapular eruption, whereas multikinase inhibitors can produce a hand-foot-skin reaction. Vemurafenib can result in squamous cell carcinomas and photosensitivity. First-generation mammalian target of rapamycin inhibitors may cause a maculopapular eruption initially involving the face and neck. Programmed death (PD)-1-ligand and receptor inhibitors are associated with bullous pemphigoid. Ipilimumab, targeting Cytotoxic -T- Lymphocyte- associated (CTLA-4) receptors, can cause a morbilliform reaction, whereas Interleukin -2 (IL-2) analogs can create the capillary leak syndrome. Chemotherapeutic drug eruptions classically can manifest in the aforementioned ways; however, it is important to understand that they are associated with myriad cutaneous adverse effects, which may be mistaken for organic skin disease. Oncologists prescribing these medications should be familiar with the cutaneous side effects of these medications, and so they may counsel patients to be on the lookout for them.

Sulfonamide Allergies.

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.

A practical 16-day desensitization protocol in lenalidomide-induced non-immediate hypersensitivity reactions

BackgroundDesensitization in immediate-type hypersensitivity reactions (HRs) caused by chemotherapeutics is well described and standardized for many drugs. However, there are no standardized protocols in non-immediate HRs. ObjectiveTo evaluate the effectiveness of a 16-day desensitization protocol in the non-immediate HRs induced by lenalidomide. MethodsAccording to our previously published slow desensitization protocol, we desensitized patients who had experienced non-immediate HRs attributable to lenalidomide. The protocol was started with the 1/100 of the daily-prescribed dose in milligrams of the culprit drug; then the doses were slowly increased to complete the procedure in 16 days. Demographic and clinical features of the patients were further appraised. ResultsTen patients (mean age was 64.7 ± 10.8 years; 7 male) were successfully desensitized to lenalidomide. The mean reaction time was 7.3 ± 3.9 days in the history, and the reaction types were delayed urticaria (n = 4), eczematous rash (n = 3), and maculopapular eruptions (n = 3). The desensitization was successfully completed in 16 days in 9 patients. In 1 patient, maculopapular eruptions developed on the 11th day, and the patient was treated with corticosteroids. We repeated the previous tolerated dose longer and completed with a slower dose increasement, and the targeted dose was achieved in 35 days. ConclusionThe 16-day desensitization protocol seemed to be safe and effective in the non-immediate type drug HRs caused by lenalidomide.

Serum soluble Fas ligand levels and peripheral blood lymphocyte subsets in patients with drug-induced maculopapular rashes, dress, and viral exanthemas

BackgroundFatty acid synthetase (Fas)/Fas ligand (FasL)-dependent apoptotic pathways have been reported as being involved in the pathogenesis of drug-induced maculopapular rashes. ObjectiveWe investigated serum soluble FasL (sFasL) levels and peripheral blood lymphocyte subtypes to discriminate maculopapular drug eruptions (MPDE) from viral exanthema (VE). Patients/methodsChildren with confirmed MPDE (group I), VE (group II), and drug rashes with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) (group III) were included. Serum sFasL levels and peripheral blood lymphocyte subtypes were analyzed in groups I–III on admission, and repeated twice (only once for group IV – controls). ResultsThere were no significant serum soluble FasL level differences among the groups for all the samples. In the initial samples, CD19+ cell numbers in group II were significantly higher than in group IV, and the CD4+/CD8+ ratio was higher than groups I and IV. In the second samples, CD4+ and CD19+ cell numbers were significantly higher in group II than group I. In the final samples, CD4+ cell numbers in group II were significantly higher than group I and group III. CD19+ cells numbers in group III were significantly lower than the other groups for all samples. ConclusionSerum sFasL levels were not found to be useful in discriminating viral exanthemas from other drug rashes. The significant differences between MPDE, VE, and DRESS were high CD4+ and CD19+ cell-count numbers in VE but low B-cell numbers in DRESS. This might be important for discriminating VE from DRESS, and the low B-cell count in early symptoms might be a useful predictor of DRESS development.