The DRESS Syndrome: A Literature Review

Fitzpatrickʼs Dermatology in General Medicine

Summary
Background Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re-exposure of patients to offending drugs.

Objectives  To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Methods  In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested.

Results  Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later.

Conclusions  PTs are useful and safe for identifying agents inducing SCAR.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjd.12125

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cea.12468

Management of allergy to penicillins and other beta‐lactams

Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.

Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests.

internal jugular vein and common carotid artery were cannulated and venoarterial ECMO was initiated (Fig. 1). Fiberoptic bronchoscopy revealed a mucous plug in the right upper bronchus, removed by aspiration. Bronchoalveolar lavage fluid (BALF) analysis showed 88% of neutrophils and 8% of eosinophils; BALF culture yielded influenza A virus. The child s respiratory function gradually improved and he was successfully weaned from ECMO after 5 days, when he required an additional 2 days of mechanical ventilation. No major complications occurred during ECMO. Serial chest radiographs showed progressive normalization. A month later, a chest computed tomography scan revealed normal lungs and bronchi and pulmonary function tests (interrupter resistance technique) showed a normal airway resistance (0.60 kPa/l·s). The range of factors associated with increased risk of asthma death include delay in diagnosis and under-treatment of disease, both long term and in the final acute event (1). Our patient had no risk factors for lifethreatening asthma. He suffered from mild intermittent asthma and the near fatal asthma exacerbation was triggered by a viral respiratory infection. Respiratory viruses are well recognized as major triggers of asthma exacerbations and a viral detection rate of 47% has been reported in children treated for near fatal asthma (4). Very few data are available on ECMO as a therapeutic option for children with life-threatening status asthmaticus (5, 6). Patients with status asthmaticus die because their condition deteriorates or because they experience treatment-associated complications. The decision to place our patient on ECMO was based on a progressive deterioration of respiratory function despite maximal medical therapy. This case indicates that even children with severe pulmonary dysfunction related to status asthmaticus may recover within a few days, if they are treated with ECMO, which allows the lungs to rest, together with standard aggressive therapies. However, as significant adverse effects may occur with ECMO, it should be reserved as rescue therapy when all other therapies fail. In conclusion, ECMO may represent a rescue therapy for children with status asthmaticus refractory to maximal conventional treatment. In addition, while it is useful for doctors and patients to recognize the features that give certain asthmatic subjects a high-risk profile, physicians should be constantly aware that no asthmatic child is really free of the risk of a life-threatening attack of asthma.

DRESS syndrome from cefadroxil confirmed by positive patch test.

Melasma is a common disfiguring condition involving acquired hyperpigmentation especially on the face, for which the pathogenesis is still uncertain, however histopathological studies showed that there is not only hyperpigmentation in the epidermis, but also solar elastosis or photo-aging due to abnormality of dermal extracellular matrix which contributes to clinical wrinkles. This study aimed to examine a link between the severity of melasma and facial wrinkles as a manifestation of photoaging in a tropical area. This study was an observational study with crosssectional design, conducted in Yogyakarta, Indonesia involving 51 patients with melasma aged 30-50 years who had fulfilled the inclusion and exclusion criteria. The melasma severity was measured clinically with the modified Melasma Severity Index (mMASI), and objectively with the Melanin Index (MI) and Erythema Index (EI) assessed with Mexameter Courage Khazaka. The wrinkle severity was measured clinically by scoring from forehead horizontal lines, crow's feet, glabellar and nasolabial lines, and total scores were obtained from all of them. The correlation analysis was done statistically with Spearman's rank tests. The results showed a weak positive but not significant correlation between the mMASI score and total facial wrinkle score (r: 0.165), and a weak positive non-significant correlation between EI and total facial wrinkle score (r: 0.06). There were significant positive moderate correlations between MI and total facial wrinkle score (r: 0.441), due to significant positive moderate correlations between MI and glabella wrinkle (r: 0.392), and between MI and nasolabial wrinkle (r: 0.339). In conclusion, a positive moderate correlation was found between MI and total facial wrinkle score, especially relating to glabellar and nasolabial wrinkles. However, there was no correlation between mMASI score and total facial wrinkle score.

/pdf/the-correlation-between-severity-of-melasma-with-facial-3fly9xh0cd.pdf

The correlation between severity of melasma with facial wrinkles in Yogyakarta, Indonesia

Mucocutaneous disorders often seen in HIV patients with varying morbidity. The HIV progression is characterized by the declining of CD4 cell counts and emergence of mucocutaneous manifestations. The aim of the study was to evaluate the relationship between CD4 cell counts with mucocutaneous manifestations in HIV patients. This was a cross-sectional study based on medical records at Dr. Sardjito General Hospital during the period January 2011-December 2015. Data of patient’s age, sex, risk factors of transmission, most mucocutaneous manifestations and CD4 cell count were gathered. The correlation between CD4 cell counts with muscocutaneous manifestations were analyzed using chi-square test. A total 928 patients were involved in the study. More than half of the patients were male (65.4%) and mostly, the patients aged 20-29 years (38.69%). The main risk factors for HIV transmission were unsafe sex (75%). The highest CD4 cell counts was 1094 cells/mm3 and the lowest was 1 cell/mm3. We found 306 cases of mucocutaneous manifestations. The most mucocutaneous manifestations was a fungal infection (40.4%) with the highest infection type was oral candidiasis(33.8%); then noninfection (28%) with the highest type was drug eruption(35.9%); and tumors(0.5%) that was only Kaposi sarcoma cases. We also found sexually transmitted infections (STIs) (18.85%) with the highest cases was condyloma acuminata (49.3%). Statistical analysis showed a significantly relationship between CD4 cell counts with a fungal infection (p 200 cells/mm3) increases the risk of viral infection by about 2.5 times and parasitic infections as much as 5 times.

https://jurnal.ugm.ac.id/bik/article/download/17066/pdf

Correlation between CD4 cell counts with mucocutaneous manifestations: study of HIV patients in Dr. Sardjito General Hospital, Yogyakarta

Setiap orangtua pasti menginginkan anak-anaknya tumbuh dan berkembang dengan baik: sehat, ceria, dan cerdas. Untuk mempersiapkan masa depan anak, ibu-ayah harus melakukannya sejak dini. Pengasuhan anak sebenarnya adalah suatu kegiatan alami yang telah dijalani manusia sejak awal adanya kehidupan. Namun di masa sekarang, tuntutan akan keahlian atau keterampilan yang harus dikuasai oleh seseorang semakin berkembang. Sebagai orangtua, kita pun berusaha agar ananda memiliki keterampilan yang membuatnya dapat mandiri dalam kehidupan sehari-hari.

Mengasah kecerdasan di usia 0-2 tahun

Human immunodefiiency virus (HIV) infection and aquired immunodeficiency syndrome (AIDS) cause a progressive depletion of CD4+ T cell populations accompanied by progressive impairment of cellular immunity and increasing susceptibility to opportunistic infections. Seborrheic dermatitis is one of the most common skin opportunistic infections on HIV/AIDS patients. Malassezia species is bilieved as the causative of seborrheic dermatitis. The aim of the study was to evaluate low CD4+ T cell counts as risk factor for Malassezia sp. infection in HIV/AIDS patients. This was an observational study with cross-sectional design conducted on HIV/AIDS patients who attended in Department of Dermatology and Venereology, Faculty of Medicine Universitas Gadjah Mada/ Dr Sardjito General Hospital, Yogyakarta and met the inclusion and exclusion criteria. Culture of Malassezia sp. was conducted in Department of Microbiology and classified as high (>100 CFU/ tape) and low ( 200 cells/mm3) and low ( 60 years were involved in the study. The number of Malassezia sp. colony on subjects with high and low CD4+ T cell counts were 31.55 ± 26.21 and 25.2 ± 33.89 CFU/ tape, respectively. No significantly relationship between between CD4+ T cell count and Malassezia sp. colony number was observed in the study (p=0.607; 95%CI=0.04-5.19; RP=0.452). In conclusion, low CD4+ T cell counts is not risk factor for Malassezia sp. infection in HIV/AIDS patients.

https://journal.ugm.ac.id/bik/article/download/7320/5710

Satiti Retno Pudjiati

Papers

DRESS syndrome from cefadroxil confirmed by positive patch test.

The correlation between severity of melasma with facial wrinkles in Yogyakarta, Indonesia

Correlation between CD4 cell counts with mucocutaneous manifestations: study of HIV patients in Dr. Sardjito General Hospital, Yogyakarta

Mengasah kecerdasan di usia 0-2 tahun

Low CD4+ T cell counts are not risk factor for Malassezia species infection in HIV/AIDS patients