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A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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

On July 23, 2022, the World Health Organization (WHO) declared the rapid global spread of Mpox (formerly known as monkeypox) a public health emergency of international concern. A 28-year-old male patient with severe Mpox infection and HIV stage 3 (AIDS) is presented., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acutely occurring, unpredictable, often life-threatening reactions that are a huge challenge in clinical practice. They are characterized by extensive blistering of skin and mucosa and are considered as one disease entity of different severity. Thus, they are summarized as SJS/TEN or EN (for epidermal or epithelial necrolysis). The diagnosis can be confirmed through synopsis of clinical pattern and histopathological findings. To identify the inducing factors, it is crucial to obtain a detailed and thorough medication and infection history. Based on the results of large epidemiological studies, potentially inducing drugs can be narrowed down even in cases of multimedication and underlying diseases. Agents with a high risk for SJS/TEN are allopurinol, antibacterial sulfonamides, non-steroidal anti-inflammatory drugs of the oxicam-type, various antiepileptics and nevirapine. They alone explain more than half of the cases of SJS/TEN. Typically, the reaction occurs during the first continuous use of the medication, while the beginning of use most often is one to four weeks prior to reaction onset. However, a drug is not always the cause of the reaction, but in approximately 70-75% of the cases very likely. In other cases infections may be potential causes. If certain medications are thought to be the inducing factors, they should be withdrawn without delay. In addition, symptomatic treatment should be initiated. In case of progression, an additional immunomodulating therapy should be considered. In this respect, systematic reviews have shown best results for cyclosporine A and systemic steroids.

The BRAF inhibitor vemurafenib was approved in 2011 for the treatment of inoperable or metastatic melanoma. Vemurafenib therapy is associated with several side effects, such as arthralgia, secondary skin tumors or inflammatory rashes. In particular cutaneous toxicities represent a serious threat to patients' adherence. Here, we present the case of a successful drug desensitization in a patient that presented with a vemurafenib-induced rash. Lymphocyte activation tests failed to detect drug-specific T cells, suggesting that the development of the rash was based upon a nonallergic drug hypersensitivity reaction. A program of slow desensitization was initiated and subsequently, vemurafenib was tolerated at the full effective and recommended dosage.

Background: Cutaneous adverse drug reactions are frequent and present with heterogenous clinical manifestations., Methods and Results: Increasingly, case reports describe drug reactions which mimic dermatoses, although exact data on prevalence are missing. Psoriasiform, lichenoid and pityriasiform exanthems are most frequent. The differentiation of these variants from the respective authentic dermatoses is difficult and only a few clinical and histological criteria are helpful. Other dermatoses like lupus erythematosus or bullous autoimmune dermatoses (pemphigus vulgaris, bullous pemphigoid) can be induced by drugs as well. These drug-triggered variations are classified as distinct subclasses of the respective dermatosis., Conclusions: Exact history and evaluation of the clinical course are essential for the diagnosis of drug reactions mimicking dermatoses and present an important challenge for the clinician. A clear-cut differentiation between the genuine dermatosis and its drug-driven simulator is not always possible.

Tyrosine kinase inhibition (TKI) such as erlotinib is a well established treatment option in the palliative care of patients with non small cell lung cancer (NSCLC). Histology and sex have been associated with different prognostic outcome measures in patients treated with erlotinib. Furthermore, the degree of rash, developed during treatment might be a relevant marker in respect to tumor response. To dissect these clinical relevant features we analysed a cohort of 275 patients treated with erlotinib in different lines of chemotherapy in our hospital. Nutrition status plays an important role in the prognosis of patients in a palliative chemotherapeutic setting, we therefore included body mass index measurements (BMI) in our analysis. We found that BMI and smoking status influence different survival patterns. Male patients have a poorer survival based on low BMI, rash development and smoking status. We therefore conclude that both nutritional and smoking status should be taken into account in the surveillance of patients with NSCLC in a palliative therapeutic setting under TKI treatment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Molecular targeted therapies - particularly epidermal growth factor receptor inhibitors (EGFRi) and multi tyrosine kinase-inhibitors (MTKi) - continually gain importance in oncology treatment. Adverse events differ greatly from those of conventional chemotherapy; especially cutaneous adverse events often constitute dose-limiting or therapy-limiting events. Knowledge of possible adverse events and close interaction between the dermatologist, the oncologist and the patient's family physician, a detailed patient education and a well-founded adverse event management are mandatory for the treatment with EGFRi and MTKi. Interdisciplinary outpatient clinics specialised on the treatment of these adverse events assist with the treatment of severe cases, the development of new therapeutic strategies and are essential for the concomitant treatment of patients treated with new targeted drugs within clinical trials., (© Georg Thieme Verlag KG Stuttgart · New York.)

Acute generalized exanthematous pustulosis (AGEP) is characterized by an acute disseminated eruption of multiple, non-follicular pustules. In addition, it can be associated with fever, elevated erythrocyte sedimentation rate, and leukocytosis. The pathogenesis of AGEP is still unknown; however, medications appear a likely cause in most cases. We report on 3 patients with AGEP demonstrating characteristic clinical and histologic features after taking amoxicillin, ampicillin, or diltiazem. All patients had positive patch test reactions to the suspected drugs.

Acute generalized exanthematic pustulosis (AGEP) is characterized by a generalized rash and sterile disseminated, sometimes coalescing subcorneal pustules. It occurs in body flexures such as the inguinal folds and intertriginous areas. The acute onset of disease is accompanied by malaise, fever > 38 degrees C and peripheral granulocytosis. We report on a female patient who according to the criteria of AGEP was diagnosed as having acute localized exanthematic pustulosis (ALEP) on the face.

Bullous drug exanthems are clinically characteristic, usually severe cutaneous and mucosal drug hypersensitivity reactions. Commonly, they appear 5-14 days after onset of drug treatment. Therapy of choice is to avoid the culprit drug and systemic administration of glucocorticoids. A key element in the immune pathogenesis of bullous drug exanthems is presumably the activation of cytotoxic CD8(+) T lymphocytes which recognize drug metabolites as nominal antigens. These compounds form spontaneously (e.g. penicillins) or are metabolized by cytochrome P450-dependent enzymes (sulfonamides). The diagnosis of bullous drug exanthems is primarily based on skin tests and in vitro-techniques. Among the skin tests, prick as well as patch tests are important. Patch tests can be also applied at the former skin lesion in fixed drug eruption. In vitro techniques include analysis of drug-specific IgE (only available for anti-penicillin, anti-sulfamethoxazole) and cellular tests with the patients' lymphocytes (lymphocyte transformation test-LTT).

There has been a remarkable progress in our understanding of the pathophysiology of hypersensitivity to contrast media (CM). Immediate reactions develop within one hour after application of CM under the clinical picture of anaphylaxis. Pruritic exanthems appearing several days afterwards account for the majority of non-immediate reactions. Current evidence indicates an allergic basis of severe immediate as well as of non-immediate reactions involving CM-reactive IgE-antibodies and T-lymphocytes, respectively. Skin tests are helpful to establish the diagnosis of these reactions. The use of skin tests to predict tolerability of CM in patients with previous hypersensitivity reaction to CM is controversial. The value of cellular in-vitro tests is unknown. In patients with previous hypersensitivity to CM, premedication with antihistamins and/or corticosteroids is recommended, but current premedication protocols do not suppress all repeat reactions. European multicenter studies addressing sensitivity, specificity and predictive value of test procedures as well as prophylaxis and risk factors of CM hypersensitivity are currently ongoing.

In all three stages, Lyme borreliosis offers a wide range of possible differential diagnoses: even the "typical" erythema chronicum migrans may present as erysipelas, erysipeloid, erythema annulare centrifugum or a drug-induced exanthema. In the advanced stages II and III, neuroborreliosis in particular may be mimicked by various other conditions of both infectious and noninfectious etiology. Major examples are CEE (Central European Encephalitis), ehrlichiosis, chlamydial infections and multiple sclerosis. Currently, the biggest diagnostic problem is the non-standardized laboratory diagnostic work-up. For this reason, even in the presence of a positive or borderline IgG antibody result, unclear symptoms should prompt a differential diagnostic investigation.

Data deriving from comprehensive hospital monitoring systems suggest that drug-induced skin effects occur in 2-5% of patients receiving any drug medication. Exanthematous (maculopapular) reaction (75%) and urticaria with/without angioedema (30%) are the most frequent of all cutaneous reactions to drugs. The incidence of cutaneous reactions relates to the quantity of the drugs which is prescribed and consumed worldwide. Thus penicillin, sulfonamides and nonsteroidal antiinflammatory drugs show the highest rate of cutaneous side effects. Drug reactions may be classified as either predictable (e.g. chemotherapy-induced alopecia) or unpredictable. Unpredictable side effects of drugs may be the result of allergic (type I to IV) or non-allergic reactions. Hereditary and acquired enzyme deficiency and variations in metabolic pathway may delay drug metabolism and cause nonallergic, toxic side effects. Such a mechanism is known to occur in patients with a low acetylation rate under hydralazine, INH or sulfonamide treatment. Some immunologic although nonallergic factors may facilitate eruptions in patients with infectious mononucleosis under ampicillin medication and in AIDS patients on co-trimoxazole therapy. When a cutaneous drug reaction is diagnosed, withdrawal of the drug is recommended. In instances in which patients display mild drug eruptions and no alternative therapy is available, the drug may be continued. However, it should be kept in mind that mild morbiliform eruption is often the initial presentation of toxic epidermal necrolysis. In AIDS patients sulfonamides most frequently have been implicated as a risk factor for the development of toxic epidermal necrolysis. In other than type 1 hypersensitivity reactions, skin testing and in vitro tests have low sensitivity and specificity.

After 18 intramuscular injections of Arumalon, a 62-year-old woman with degenerative hip-joint changes developed a severe illness with fever up to 39 degrees C, swellings of the finger, hand and knee joints, as well as a local skin rash and changes in the blood (WBC 1900/microliters, platelets 113,000/microliters), and increase in liver enzymes (GOT 83 U/l, GPT 93 U/l, lactate dehydrogenase 693 U/l). Arumalon, a glucosaminoglycan-peptide complex containing a watery extract of bovine cartilage and bone marrow, is used as a cartilage-protecting medication. The close temporal relationship between the injections and the symptoms suggested that the illness was drug-induced. This view was supported by a positive lymphocyte transformation test with Arumalon and its constituents, as well as by the demonstration of Arumalon-specific antibodies in the cultured lymphocyte fluid while the serum was negative for the antibodies. The illness took a protracted course. The patient became completely free of symptoms only after a year on a maintenance dose of prednisone, 15 mg daily. As a local inflammatory reaction was noted at the very start of the Arumalon injections, presensitization against the foreign proteins in Arumalon cannot be excluded. This is also supported by the fact that the specific lymphocyte proliferation was essentially unchanged even after nine months. This case illustrates the importance of careful assessment of increased and repeated manifestations of local reaction during Arumalon treatment, in particular in view of the risk of systemic side effects.

It is casuistically reported on a severe drug allergy of the immediate type compared with chloral hydrate. The unusually manifold allergic symptomatology allows a classification into the feature of the allergic mononucleosis.

Aminoglutethimide was applied for treatment of 10 patients (8 postmenopausal, 2 ovariectomized) with metastasizing breast cancer. The patients were extensively pretreated with cytostatic and hormonal measurements and already completely resistant to these therapies. Using aminoglutethimide (500-1000 mg daily) plus additional substitution with 20-40 mg hydrocortisone one complete and three partial remissions could be achieved. Stabilization was observed in 3 cases. The duration of remission varied between 4-8 months in 3 cases and lasted one month in a further patient.

In 257 patients with primary or secondary infertility, tubal occlusion or impeded tubal patency was found. The patients received Bactrim or Tandearil and the tubal patency was retested. In a control group of 74 cases, 2 tubal patency tests were done without treatment. Following treatment with Bactrim, 40,4% of the previously occluded fallopian tubes were patent. Following treatment with Tandearil, 34% of the previously occluded tubes were patient. In the non-treated group, 25% of the cases showed tubal patency at the second patency test. The results were more striking for the cases with impeded tubal patency. The success rate was 73,3% following treatment with Bactrim, 50% following treatment with Tandearil and 26,7% in the untreated control group.

Side effects of non-steroidal antiinflammatory drugs are divided in three groups: unwanted effects resulting from the inhibition of prostaglandin synthesis, side effects specific for certain drugs, and side effects due to application of drugs in general. Prior to the prescription of non-steroidal antiinflammatory drugs the risk of side effects has to be balanced against the expected benefits, the patient has to be informed about possible side effects and their symptoms.

Side effects of chrysotherapy in 268 patients with rheumatoid arthritis, are reported. The incidence of side effects of all drugs used (Sodiumaurothiosulfate, Aurothiopolypeptide, Sodiumaurothiomalate) was approximately equal. The most common side effects were eosinophilia, exanthema, itching, albuminemia and leukopenia.

A drug eruption with subcorneal pustulation is presented, occurring in a patient during treatment with eprazinone . The biopsy of the initial lesions showed changes as in pustulosis subcornealis . The aetiopathogenetic relationship between administration of eprazinone and the pustular eruption was confirmed by patch test.

Symptoms similar to phenomena in immunologic diseases but without specific reactions are classified as pseudo-immunologic. They are caused, especially when allergoid, by complement-activation via the alternate pathway or are due to a lack of inhibitors. Other symptoms are based upon receptor-substrate interactions or enzymatic deficiency. Diagnosis is confirmed by characterization of the pathogenic mechanisms and by missing immunological phenomena. In the majority of cases therapy is similar to measures in true immunologic diseases. Prophylaxis by substitution is only possible in a few situations.

Receptor research is a rather new but most promising field of research. This review summarizes the data available on the adrenergic receptors. in addition, information is provided about the important function of these membrane receptors as control or modulator of dermatophysiology and dermatopathy.

A maculopapular exanthema developed in a 60-year-old man with coronary heart disease while being treated for angina with the calcium antagonist diltiazem. Epicutaneous and scratch tests were positive, both for the immediate type (type I) and the delayed type (type IV), proving that the drug had caused the allergic reaction. The exanthema quickly disappeared once the drug had been discontinued. Anti-anginal treatment was continued without further complications with nifedipine.

The present paper gives a review of the data published in Poland concerning side effects of drugs. The most numerous observations concern antibiotics (particularly penicillin), sulfonamides, salicylates and antitetanic serum. The most frequent complications were: shock, urticaria, erythema multiforme and exanthema maculopapulosum.

Cutaneous side effects due to beta-adrenoreceptor-blocking agents are clinically polymorphous. Apparently they appear after several months of continuous therapy. Atypical psoriasiform, lichen planus-like, and eczematous "chronic" rashes are mainly observed. The histological picture usually corresponds to a lichenoid drug reaction. More rarely the so-called pseudo-lupus erythematodes-syndrome is found, which cannot be differentiated from the "idiopathic" disease. Noteworthy extracutaneous manifestations are fibrosing processes, which may be irreversible. Pathogenetically, a delayed hypersensitivity reaction, and an action on the epidermal chalone system (epinephrine-adenylcyclase-c-AMP-complex) may be assumed. Consequently, continuous observation of the skin and mucous membranes is necessary, and medication should be withdrawn if cutaneous side-effects appear.