Exanthematous Skin Research Articles

Cutaneous adverse drug reactions

Background: Cutaneous adverse drug reactions are common and produce easily identifiable clinical symptoms. These may range from mild maculopapular rashes to severe reactions associated with systemic disease.Current Concepts: The most common presentation of a drug eruption is in the form of a maculopapular rash or exanthematous skin eruption, followed by fixed drug eruptions and urticaria. Severe cutaneous adverse drug reactions include Stevens-Johnson syndrome/toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, which are rare but potentially life-threatening. Recently, it has emerged that cutaneous adverse drug reactions associated with newly developed drugs, such as epidermal growth factor receptor inhibitors, may induce a variety of cutaneous manifestations.Discussion and Conclusion: Although certain drugs, such as antimicrobials and anticonvulsants, can frequently cause drug eruptions, their effects may change, depending on the situation and timing. Therefore, in order to resolve symptoms and prevent complications, early diagnosis, drug identification, and appropriate treatment should be performed, in consideration of the various factors involved.

Pityriasis Rosea Gibert - Disease History and New Findings

The author's aim in this article is to describe a common exanthematic disease typical of adolescence, pityriasis rosea Gibert, in the light of new findings. Another aim is to draw attention to an overlooked fact about the difficulty and inconsistency of therapy with the recommended course of action. The author uses his own experience from his many years of dermatological practice and adds facts from current literature sources on the disease. The meaning of the disease name is explained and the historical implications of the disease name are clarified. The current view of its probable viral etiopathogenesis and its similarity to another exanthematous skin disease, exanthema subitum, are described. The prodromal stage of the disease and the clinical picture of the skin findings with characteristic seeding of lesions resembling "Christmas tree branches" are described. The author's clinical pictures of the findings in individual patients with this disease are included. The possible relationship with COVID-19 is noted. The differential diagnosis is discussed, including the similarity to secondary syphilis, and the uncharacteristic histopathological picture of the disease is described. Finally, treatment options are discussed, with the caveat that the very common use of topical corticosteroids is not very effective and rather non-corticoid external therapy is recommended. The author draws attention to the possible alteration of the psychological state of predominantly adolescent patients due to the frequent long persistence of cutaneous, and therefore visible, symptoms.

Coexisting Pediatric Acute Generalized Exanthematous Pustulosis and Staphylococcal Scalded Skin Syndrome

Acute Generalized Exanthematous Pustulosis is a rare drug-induced skin disorder that can present at any age. It is typically noted by swelling and erythema, with numerous facial and/or anogenital nonfollicular pustules that quickly disseminate. Staphylococcal scalded skin syndrome presents with erythema and swelling that similarly favor the head and intertriginous sites with subsequent bullae formation. We present a case of a four-year-old female who presented with SSSS complicated by the development of AGEP and discuss the course of her condition and treatment.

Pityriasis Rosea: An Updated Review.

Pityriasis rosea is a common acute, self-limited papulosquamous dermatosis that primarily affects children and young adults. The condition and its clinical variants may pose a diagnostic challenge, especially in the absence of the herald patch. This article aimed to familiarize pediatricians with clinical manifestations, evaluation, diagnosis, and management of pityriasis rosea. A search was conducted in March 2020 in Pubmed Clinical Queries using the key term " pityriasis rosea". The search strategy included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies, and reviews (including narrative reviews and meta-analyses) published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Pityriasis rosea occurs mainly in individuals between 10 and 35 years of age with a peak during adolescence. Human herpesvirus (HHV)-7 and HHV-6 have been implicated as the causative agents in some patients with pityriasis rosea. A mild prodrome consisting of headaches, fever, malaise, fatigue, anorexia, sore throat, enlarged lymph nodes and arthralgia is present in about 5% of patients. The most common presenting sign, found in approximately 80% of patients, is a "herald" or "mother" patch which is larger and more noticeable than the lesions of the later eruption. A generalized, bilateral, symmetrical eruption develops in approximately 4 to 14 days and continues to erupt in crops over the next 12 to 21 days. Typical lesions are 0.5 to 1 cm, oval or elliptical, dull pink or salmon-colored macules with a delicate collarette of scales at the periphery. The long axes tend to be oriented along the skin lines of cleavage (Langer lines). Lesions on the back may have a characteristic "Christmas tree", whereas lesions on the upper chest may have a V-shaped pattern. There are many conditions that may mimic pityriasis rosea. Pityriasis rosea in the absence of the herald patch and its variants may pose a diagnostic challenge. The typical course is 6 to 8 weeks. In the vast majority of cases, reassurance and symptomatic treatment should suffice. Active intervention may be considered for individuals with severe or recurrent pityriasis rosea and pregnant women with the disease. Treatment options include acyclovir, macrolides (in particular, erythromycin), and ultraviolet phototherapy. If active intervention is needed, there is evidence supporting the use of oral acyclovir to shorten the duration of illness. Pityriasis rosea is a common, acute, self-limiting exanthematous skin disease that primarily affects children and young adults. The condition is characterized by a "herald patch" after which oval erythematous squamous lesions appear along Langer's lines of cleavage on the trunk and proximal extremities, giving it a "Christmas tree" appearance. The disease presenting in its classical form can easily be diagnosed. Clinical variants of the disease may pose a diagnostic challenge for the general pediatrician. Knowledge of the disease is essential to allow prompt diagnosis and to avoid unnecessary investigations.

Linear patterns of the skin and their dermatoses.

Knowledge about the linear patterns of the skin is a key competence of dermatologists. Four major groups of linear patterns can be distinguished: Langer lines, dermatomes, Blaschko lines and exogenous patterns. Langer lines run in the direction of the underlying collagen fibers (least skin tension) and play an important diagnostic role for some exanthematous skin diseases. In the thoracodorsal region, the distribution of the Langer lines gives rise to what is referred to as a 'Christmas tree pattern'. A dermatome is an area of skin that is supplied by a single spinal nerve. Disorders with a neuronal origin follow this pattern of distribution. The lines of Blaschko delineate the lines of migration of epidermal cells during embryogenesis. Exogenous linear patterns are caused by external factors. The present CME article will highlight important skin disorders that primarily present in the form of one of the aforementioned patterns. In addition, we will also address skin conditions that may secondarily follow with these patterns (or distinctly not do so) as the result of various mechanisms such as the Koebner phenomenon, reverse Koebner phenomenon, and Wolf's isotopic response.

Molecular characterization of Orf virus isolates from Kodai hills, Tamil Nadu, India.

Aim:The present study was carried out to find out the causative agent of exanthematous skin lesions in sheep maintained by Southern Regional Research Centre, Mannavanur, Kodai hills, Tamil Nadu.Materials and Methods:Polymerase chain reaction (PCR) with Orf virus (ORFV) B2L gene-specific primers was carried out by employing the total genomic DNA isolated from the scabs as the template. The ORFV isolates from Kodai hills were characterized by the use of bioinformatics tools.Results:The amino acid identity of ORFV isolate 1 from Kodai hills is having 98.14%, 96.29%, and 83.59% identity with reference strains of ORFV, Pseudocowpox virus, and bovine papular stomatitis virus, respectively. Phylogenetic analysis revealed that ORFV isolates from Kodai hills clustered with the other ORFV isolates from different geographical areas of India.Conclusion:The etiological agent of exanthematous skin lesion among sheep of Kodai hills is ORFV.

Radiocontrast Media Hypersensitivity: Skin Testing Differentiates Allergy From Nonallergic Reactions and Identifies a Safe Alternative as Proven by Intravenous Provocation

Hypersensitivity reactions occurring within minutes after intravascular injection of iodinated radiocontrast media (RCM) are not rare and have been previously considered to be nonallergic. However, in the last decades, evidence is increasing that genuine RCM allergy may present as either full-blown anaphylaxis or delayed exanthematous skin reaction. We aimed to assess whether allergy diagnostics including skin and provocation testing can differentiate between nonallergic and allergic RCM hypersensitivity by identifying the causative RCM as well as tolerated alternative RCM. We retrospectively evaluated clinical and diagnostic data from 45 consecutive patients with RCM hypersensitivity. Immediate nonallergic RCM hypersensitivity was diagnosed in 21 patients, immediate-type RCM allergy in 11, delayed-type RCM allergy in 11, and delayed-type iodine allergy in 2. All patients with immediate-type RCM allergy had a history of moderate to severe anaphylaxis. Eleven of 13 patients with delayed-type allergic reactions including the 2 cases of iodine allergy suffered from maculopapular exanthem developing several hours to days after exposure, 1 was a systemic hypersensitivity syndrome, and 1 a fixed drug eruption. Of 18 RCM-allergic patients tested, all tolerated an alternative RCM in the intravenous provocation. The diagnostic sensitivity of intradermal RCM testing to identify allergic patients is high in both immediate-type and delayed-type RCM allergy. Intravenous provocation with a skin test-negative RCM is safe and enables identification of a tolerated alternative RCM. Additional skin testing of iodine solution is required to identify patients with iodine allergy.

Differential diagnosis of late-type reactions to injected local anaesthetics: Inflammation at the injection site is the only indicator of allergic hypersensitivity.

Anaphylaxis-like reactions developing within a few minutes are the most frequent complications of subcutaneous or submucosal injections of local anaesthetics (LAs), and topically applied LAs are potential contact allergens. In addition, injected LAs have been reported to induce delayed reactions, including local inflammation at the injection site, and various general symptoms. To assess the frequency and symptoms of late-type hypersensitivity occurring several hours after LA injections. We retrospectively evaluated clinical data and test results from all patients referred to our allergy clinic in a period of 20 years for diagnostic work-up of LA-associated late-type reactions. Of 202 patients reporting symptoms with onset at least 1 hour after LA injection, 40 had cutaneous inflammation confined to the injection site, and 162 reported various systemic symptoms. LA hypersensitivity could be excluded in all patients with systemic complaints by means of skin testing and subsequent subcutaneous provocation. In 8 of the 40 patients (20%) with local inflammatory reactions, late-type allergic LA hypersensitivity was confirmed. Late-type LA allergy commonly causes inflammatory skin reactions confined to the injection site. Conversely, LAs are highly unlikely to trigger delayed systemic symptoms such as urticarial or exanthematous skin eruptions.

Penicillin allergy – recommendations for diagnostic work up and patient management

Allergy to penicillins or cephalosporins manifests either within a few minutes after intake or infusion in the form of acute anaphylaxis symptoms, or several hours to days later as exanthematous skin reactions. Exanthematous skin eruptions caused by amoxicillin or ampicillin are currently the most frequently diagnosed clinical reaction pattern within the spectrum of penicillin allergy. Certain single cephalosporins such as cefazolin, ceftriaxone, and cefuroxime are gaining in relevance as triggers of β‑lactam antibiotic-induced IgE(Immunglobulin E)-mediated anaphylaxis reactions. This article provides an overview of selected scientific articles and is based on research in PubMed, studies, and specialist databases. Penicillin allergy work-up is based on patient history and documented medical findings; serological IgE determinations, as well as skin and provocation testing, are routinely performed. While the determination of IgE directed to certain penicillin determinants is one of the few reliable laboratory tests for the diagnosis of drug hypersensitivity, the basophil activation test or the lymphocyte transformation test are reserved for experienced laboratories which are able to critically evaluate their test results. Wheal-and-flare reactions in skin prick and intradermal testing suggest IgE-mediated allergy, while infiltrated erythematous or exanthematous plaques in patch or intradermal testing point to delayed-type hypersensitivity. The overall predictive value of combined in vitro and in vivo allergy testing with β‑lactam antibiotics is approximately 90%. However, subsequent controlled provocation testing is recommended in order to reliably exclude allergic hypersensitivity.

“Treating Through” Decision and Follow-up in Antibiotic Therapy-Associated Exanthemas

Immediate discontinuation or replacement of suspected drugs is considered standard medical care in acute exanthematous skin reactions. In the treatment of bacterial infections, structurally different alternative antibiotics, however, are commonly second choice options due to a suboptimal antimicrobial activity or an unfavorable side effect profile. Nonetheless, "treating through," the continuation of antibiotic treatment despite an objective exanthema, is practiced only rarely. We aimed to assess whether "treating through" is an option for patients with severe bacterial soft tissue infections (severe cellulitis) who experience maculopapular exanthema (MPE) during antibiotic therapy. We retrospectively reviewed clinical data from 18 patients who developed MPE within a few days after initiation of intravenous antibiotic treatment. A decision to "treat through" was made when the suspected antibiotics (β-lactams, clindamycin, ciprofloxacin) were clinically effective and the benefits of continued treatment outweighed potential risks. Clinical and laboratory findings were closely monitored in an inpatient setting. In 2 patients, a modification of antibiotic therapy was deemed necessary due to a significant increase of liver enzymes within 4 days after the initial decision to "treat through." Because of a progression of MPE under ongoing treatment with cefuroxime and clindamycin, clindamycin was discontinued in 1 patient. In another 3 patients, antibiotic treatment was modified because of insufficient improvement of the soft tissue infection. In the remaining 12 "treated through" cases, the skin symptoms improved despite unchanged continued antibiotic treatment, and relevant laboratory parameters remained within the normal range. Careful risk-benefit assessment may enable the continuation of antibiotic therapy despite MPE, provided that patients are under close medical observation.

Multiplex PCR for rapid diagnosis and differentiation of pox and pox-like diseases in dromedary Camels.

BackgroundPox and pox-like diseases of camels are a group of exanthematous skin conditions that have become increasingly important economically. Three distinct viruses may cause them: camelpox virus (CMLV), camel parapox virus (CPPV) and camelus dromedary papilloma virus (CdPV). These diseases are often difficult to differentiate based on clinical presentation in disease outbreaks. Molecular methods such as PCR targeting species-specific genes have been developed and used to identify these diseases, but not simultaneously in a single tube. Recently, multiplex PCR has gained reputation as a convenient diagnostic method with cost-and timesaving benefits.Methods and resultsIn the present communication, we describe the development, optimization and validation of a multiplex PCR assay able to detect simultaneously the genome of the three viruses in one single test allowing for rapid and efficient molecular diagnosis. The assay was developed based on the evaluation and combination of published and new primer sets and was validated with viral genomic DNA extracted from known virus strains (n = 14) and DNA extracted from homogenized clinical skin specimens (n = 86). The assay detects correctly the target pathogens by amplification of targeted genes, even in case of co-infection. The method showed high sensitivity, and the specificity was confirmed by PCR-product sequencing.ConclusionThis assay provide rapid, sensitive and specific method for identifying three important viruses in specimens collected from dromedary camels with varying clinical presentations.

Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions.

Hydranencephaly: A rare cause of an enlarging head size in an infant

Hydranencephaly: A rare cause of an enlarging head size in an infant

Role of T cells in nonimmediate allergic drug reactions

This review presents the current knowledge of the role of T cells in drug allergy manifesting as exanthematous, pustular and bullous skin diseases, collectively referred to as nonimmediate allergic drug reactions. Both CD4+ and CD8+ T cells producing type 1 and type 2 cytokines and endowed with cytotoxic properties are involved in nonimmediate allergic drug reactions. Recent studies have confirmed that CD8+ T cells play a major role in the pathophysiology of nonimmediate allergic drug reactions, and have characterized new cytotoxic molecular pathways responsible for the severity of the bullous forms of nonimmediate allergic drug reactions. Nonimmediate allergic drug reactions are mediated by T cells and mostly affect the skin. Nonimmediate allergic drug reactions comprise several diseases ranging from the frequent and benign maculo-papular exanthema to the severe and rare toxic epidermal necrolysis. Progress in the knowledge of the pathophysiology of nonimmediate allergic drug reactions comes from a better understanding of the mechanisms of drug recognition by T cells and from a careful analysis of the phenotype and functions of CD4+ and CD8+ T cells infiltrating the skin lesions. Recent studies have confirmed that the different clinical forms of nonimmediate allergic drug reactions are associated with distinct types of T cell-mediated skin inflammation. However, CD8+ T cells appear as major effector T cells in most of the nonimmediate allergic drug reactions. Future studies to analyze the early cellular and molecular events leading to the development of the allergic skin reaction will be helpful in order to define diagnostic and therapeutic targets.

Dermatoscopic Findings of Cutaneous Mastocytosis

Background: Mastocytosis is a disorder characterized by the accumulation of mast cells in various organs, most commonly in the skin. Cutaneous mastocytosis (CM) can be classified as nodular CM with solitary or multiple lesions, diffuse CM (erythroderma), and maculopapular CM including the papular/plaque variant, urticaria pigmentosa (UP) and telangiectasia macularis eruptiva perstans (TMEP). Objective: To evaluate the dermatoscopic features of cutaneous mastocytosis. Methods: We reviewed the dermatoscopic images of 6 patients who had different variants of cutaneous mastocytosis and who attended the Departments of Dermatology at the Medical University of Ankara, Turkey, and the Medical University of Vienna, Austria. Results: In UP and in the papular variant of CM the most common structures seen by dermatoscopy were brown reticular lines (pigment network). In TMEP we observed telangiectatic vessels arranged in a reticular pattern. Conclusion: Skin lesions of mastocytosis may exhibit a pigment network, a dermatoscopic feature said to be characteristic of melanocytic lesions. We were also able to identify a new dermatoscopic feature, a reticular vascular pattern that is characteristic of a clinical variant of mastocytosis known as TMEP. This feature may help to differentiate TMEP from other variants of mastocytosis and from other exanthematous skin diseases.

Management of hypersensitivity reactions to iodinated contrast media

All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE‐mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T‐cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM‐induced hypersensitivity reactions in the future.

Polymorphisms of High-Affinity IgE Receptor and Histamine-Related Genes in Patients with ASA-Induced Urticaria/Angioedema

The pathogenic mechanism of ASA-induced urticaria/angioedema (AIU) is still poorly understood, but it has been known that histamine releasing by cutaneous mast cell activation is considered to be an important role. Considering the importance of histamine in AIU, we speculated that a genetic abnormality of histamine-related genes such as a high-affinity IgE receptor, a metabolic enzyme of histamines and histamine receptors, may be involved in the development of AIU. Enrolled in the study were 110 patients with AIU, 53 patients without ASA hypersensitivity who had various drug allergies presenting as exanthematous skin symptoms, and 99 normal healthy controls (NC). Eleven single nucleotide polymorphisms (SNPs) of the β chain of the high-affinity IgE receptor (FCER1B) and three histamine-related genes-histamine N-methyltransferase (HNMT), histamine H1 receptor (HRH1), histamine H2 receptor (HRH2)-were screened using the SNP-IT assay based on a single base extension method. No significant differences were observed in allele and genotype frequencies, and haplotype frequencies of all the SNPs of FCER1B, HNMT, HRH1, and HRH2 among the three groups (p>0.05, respectively). These results suggest that the polymorphisms of FCER1B and the three histamine-related genes may not contribute to the development of AIU phenotype in the Korean population.

The role of human herpes virus 6 and 7 in the pathogenesis of pityriasis rosea.

Pityriasis rosea (PR) is an acute exanthematous inflammatory skin disease in which many epidemiological studies suggest a viral infection in its pathogenesis. Several viruses such as picornaviruses, parvoviruses and herpes viruses were accused as causative agents in PR. Human herpes virus-6 (HHV-6) and HHV-7 are newly discovered members of herpesviridae family. Several diseases including roseola infantum and PR have been linked with HHV-6 and HHV-7 in dermatology. We aimed to investigate the role of HHV-6 and HHV-7 in the pathogenesis of PR. Blood samples from 35 patients with acute PR and 30 healthy volunteers were examined to obtain titres for HHV-6 and HHV-7 antibodies. Anti-HHV-6 and -HHV-7 immunoglobulin (Ig) G antibodies were detected by IFA. The high titres of anti-HHV-6 IgG were determined in four patients and anti-HHV-7 IgG in only two of four patients. In our study, we haven't found any significant relationship between HHV-6, HHV-7 and PR. Our results were supported with the data of several previous studies.

Involvement of T cells in drug-induced allergies.

The current understanding of drug-induced allergy is mainly based on the hapten model. This model may be relevant for the initiation of various severe forms of drug-induced allergy, but does not explain other features of drug-induced allergy. Our model of direct metabolism-independent drug recognition by activated T cells supplements the hapten model and appears to be relevant in various clinical situations, in particular in transient exanthematous skin reactions.

Unerwünschte Arzneimittelreaktionen bei gleichzeitiger Gabe von hochdosiertem Phenobarbital und Betalaktam-Antibiotika

The present paper reports on a striking increase in undesirable drug induced reactions during simultaneous administration of high-dosage phenobarbital and beta-lactam antibiotics to children in intensive care. In a 30-month study period, reactions which had to be classified as drug-induced were seen in 24 out of a total of 49 children (mainly exanthematous skin reactions, in some cases severe). The complications were mainly observed in patients receiving a combination of cefotaxime and phenobarbital. Etiologically, a toxic reaction to the combination of hepatically metabolized beta-lactam antibiotics with an enzyme-inducing drug must be considered in addition to the allergenic potential of the individual components.