Ágnes Kinyó

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization

BackgroundIt hasn’t been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis.MethodsTen patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin’s main antigens.ResultsLymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients.ConclusionsOur data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Strontium ranelate-induced DRESS syndrome with persistent autoimmune hepatitis

A relatively new drug used in the treatment of osteoporosis, strontium ranelate has been associated with several side effects, including increased relative risk of venous thromboembolism (including pulmonary embolism), transient increases in creatine kinase levels, mild gastrointestinal, nervous system and muscular disorders, and drug-induced hypersensitivity syndrome, also called DRESS syndrome (1). DRESS syndrome is a severe, acute drug reaction defined by the presence of fever, skin eruptions and systemic symptoms, including enlarged lymph nodes, abnormal liver function, renal impairment, and pulmonary and cardiac infiltrates, as well as haematological abnormalities, primarily hypereosinophilia and lymphocytosis (2, 3). We report here a case of a patient with strontium ranelate-induced DRESS who developed persistent autoimmune hepatitis.

A mutational hotspot in CYLD causing cylindromas: A comparison of phenotypes arising in different genetic backgrounds

Brooke-Spiegler syndrome (BSS; OMIM 605041) has been described as an autosomal dominant disease characterized by the development of a wide variety and number of skin appendage tumours not commonly found in the general population, such as cylindromas, trichoepitheliomas and spiradenomas (1, 2). The tumours grow slowly in size and number throughout life and may give rise to a large confluent mass on the head, historically referred to as turban tumours (1, 2). The gene responsible for BSS, the cylindromatosis gene (CYLD), is localized on 16q12-q13 (2). So far more than 79 mutations have been identified, with clustering at the 3’ end of the CYLD gene, which encodes for the catalytic (exons 8–20) (3, 4). These mutations have been identified in patients with phenotypic features of either BSS, familial cylindromatosis (FC; OMIM 132700) or multiple familial trichoepithelioma type 1 (MFT1; OMIM 601606), suggesting that these 3 syndromes are phenotypic variations of the same genetic disease (5, 6). A Hungarian pedigree from Bukovina (Romania) affected by BSS and an English pedigree from northern England were included in this study.

A novel missense mutation of the CYLD gene identified in a Hungarian family with Brooke–Spiegler syndrome

Brooke–Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease characterized by skin appendage tumors due to mutations in the cylindromatosis gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members, father and daughter. Direct sequencing demonstrated a novel missense mutation (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin‐specific protease domain of the encoded protein. We performed preliminary analysis to reveal the functional role of this novel mutation. Our data suggest that this novel CYLD mutation leads to increased ubiquitination of NEMO through influencing deubiquitinating activity of the CYLD protein and thus may result in enhanced NF‐κB signalling.

A newly identified missense mutation of the HR gene is associated with a novel, unusual phenotype of Marie Unna Hereditary Hypotrichosis 1 including limb deformities.

Marie Unna Hereditary Hypotrichosis 1 (MUHH1; OMIM 146550), a rare monogenic condition characterized by the development of sparse, twisted hair or complete hair loss, is the consequence of mutations located in the hairless (HR) gene. We have identified a 68-year-old Hungarian woman affected by alopecia universalis and limb deformities of all four extremities. Direct sequencing of the coding regions of the HR gene revealed a novel missense mutation in the third exon of the HR gene (c.974G/A, p.Gly325Asp). The affected family member carried the mutation in a heterozygous form, while the only available, clinically unaffected family member (the son of the patient) and the unrelated controls carried the wild type sequence. The association between the presence of HR gene mutations and the development of alopecia is well-established, however, further studies are needed to elucidate the putative role of this novel HR mutation in the development of limb deformities.

COP1 contributes to UVB-induced signaling in human keratinocytes

UVB irradiation has been shown to trigger a broad range of changes in gene expression in human skin; however, factors governing these events are still not well understood. In this study, we show that human constitutive photomorphogenic protein-1 (huCOP1), an E3 ligase, contributes to the orchestration of UVB response of keratinocytes. Accordingly, our data show that (i) huCOP1 protein is expressed both in the nucleus and in the cytoplasm of cultured keratinocytes, (ii) UVB reduces the levels of the huCOP1 mRNA and protein, and (iii) induces changes in the subcellular localization of huCOP1. Finally, we show that gene-specific silencing of huCOP1 induces the accumulation of the tumor suppressor p53 protein, which is further increased after UVB irradiation.

Allopurinol-induced hypersensitivity syndrome

UNLABELLED Allopurinol is an effective urate lowering drug, which is usually well-tolerated with no adverse effects in most cases, but about 2% of the treated patients develop a skin rash, and patients may experience severe allopurinol-induced hypersensitivity syndrome. AIMS The aim of the authors was to summarize and present the clinical manifestations of allopurinol-induced hypersensitivity in patients treated at the Department of Dermatology and Allergology, University of Szeged in order to identify potential associations with this syndrome. METHODS Retrospective review of all patients who were referred to the department with allopurinol-induced hypersensitivity syndrome in the last four years. RESULTS During four years, 11 patients were treated with allopurinol-induced hypersensitivity syndrome. The average age was 70.3 years. Before the initiation of allopurinol therapy, 36% of patients had already suffered from various degrees of renal impairment, and 72% of them had been taking thiazide diuretics. Cutaneous manifestations were mainly generalized, erythematous, maculopapular exanthemas (9 patients, 82%), and two patients showed signs of erythema multiforme (18%). Asymptomatic hyperuricemia was the indication for allopurinol therapy in all patients. CONCLUSIONS Allopurinol-induced hypersensitivity syndrome is a severe, life-threatening disease. Administration of allopurinol should be initiated with clear indications in appropriate dose. Old age, underlying renal impairment and concomitant thiazide diuretic intake should be considered as potential risk factors for developing hypersensitivity syndrome.

Antibiotic Induced Cutaneous Rash in Infectious Mononucleosis: Overview ofthe Literature

Katinka Onodi-Nagy1*, Zsuzsanna Bata-Csorgő1, Erika Varga1, Lajos Kemeny1 and Agnes Kinyo1,2 1Department of Dermatology and Allergology, University of Szeged, Albert Szent-Gyorgyi Medical Center, Hungary 2Department of Dermatology, Venereology and Oncodermatology, University of Pecs, Hungary *Corresponding author: Katinka Onodi-Nagy, Department of Dermatology and Allergology, University of Szeged, Albert Szent-Gyorgyi Medical Center, 6 Koranyi fasor, 6720 Szeged, Hungary, Tel: +36-62-54-52-77; Fax: +36-62-54-59-54; E-mail: onodikatinka@gmail.com

UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes

Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human ortholog of the Arabidopsis thaliana constitutive photomorphogenesis 1 (COP1) protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a posttranslational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes. In this study, we report that stable siRNA-mediated silencing of huCOP1 affects the UVB response of several genes within 2 h of irradiation, indicating that altered huCOP1 expression sensitizes the cells toward UVB. Pathway analysis identified a molecular network in which 13 of the 30 examined UVB-regulated genes were organized around three central proteins. Since the expression of the investigated genes was upregulated by UVB in the siCOP1 cell line, we hypothesize that huCOP1 is a repressor of the identified pathway. Several members of the network have been implicated previously in the pathogenesis of non-melanoma skin cancers; therefore, clarifying the role of huCOP1 in these skin diseases may have clinical relevance in the future.