Phytomenadione pre-treatment in EGFR inhibitor-induced folliculitis.

BACKGROUND: Targeted oncology therapy with inhibitors of epidermal growth factor receptor is associated with numerous cutaneous side effects. Acneiform eruptions are the most frequent skin toxicities reported. They may lead to impairment of patients' quality of life and sometimes may even become severe enough to necessitate the interruption or cessation of therapy. OBJECTIVE: To assess the possible effect of topical phytomenadione (vitamin K1 ) pre-treatment in diminishing the extent and severity of acne-like follicular rash associated with epidermal growth factor receptor inhibitor therapy. METHODS: A series of 20 patients with colorectal cancer or head and neck cancer were pre-treated with phytomenadione cream (0.05% in seven patients and 0.1% in 13 patients), starting morning before the first infusion of cetuximab or panitumumab, and followed up for the development of therapy-associated folliculitis. The cream was prepared from phytomenadione solution added to a hydrophilic cream base, oil in water, to obtain the concentration of 0.05% or 0.1%. RESULTS: Majority of patients (15 out of 20, 75%) pre-treated with phytomenadione cream experienced only mild, grade I acneiform eruptions. Five patients (25%) had grade II rash, which included two of seven patients pre-treated with 0.05% phytomenadione cream and three of 13 patients who used 0.1% phytomenadione cream. Topical phytomenadione cream was well tolerated and no abnormalities in blood coagulation were observed. CONCLUSIONS: Topical pre-treatment with phytomenadione cream might become useful in epidermal growth factor inhibitor-associated acneiform eruptions.

Segmental Darier's disease postpartum and following tubal ligation.

Segmental Darier's disease is a rare clinical variant of autosomal dominant Darier's disease (keratosis follicularis) exhibiting eruptions in a unilateral arrangement following the lines of Blaschko. It occurs in approximately 10% of patients with Darier's disease. We report two cases of type 1 segmental Darier's disease that appeared a few months after childbirth; in one case, recurrence of the disease occurred after tubal ligation.

Cetuximab-induced cutaneous toxicity.

BACKGROUND: Epidermal growth factor receptor inhibitors are recently utilized by oncologists in advanced cases of certain malignancies. However, these agents are associated with numerous cutaneous adverse reactions. OBJECTIVE: To systematically review the cutaneous toxicity of cetuximab-treated patients. METHODS: An analysis of a series of 24 patients (20 men and 4 women) treated with cetuximab (12 patients with head and neck cancer and 12 patients with colorectal cancer) was performed with respect to relevant clinical characteristics. RESULTS: A total of 22 patients (91.7%) developed pustular or maculopapular follicular eruption, often referred to as acneiform rash. One patient (4.2%) developed paronychia in the course of cetuximab therapy. All patients with head and neck cancer had a combination treatment with radiotherapy and experienced radiation dermatitis accompanied by skin xerosis. Anaphylactic reaction was observed in three patients (12.5%). CONCLUSIONS: The most frequent cutaneous side effect reported in this series was acneiform eruption. The authors observed that all women with acneiform rash had only limited facial involvement, whereas all but one man experienced more widespread lesions of the face, the back and the chest. We found no association between the extent and severity of cutaneous eruptions (grade 1 vs. grade 2) and patients' response to therapy.

Expression pattern of the bcl-2 homologous protein bad in normal skin, psoriasis vulgaris and keratinocytic tumors.

Previous investigations focused on the mechanisms and regulation of apoptotic process have found that bcl-2 and its homologous proteins are central regulators of the mitochondrial phase of apoptosis. Expression of several members of the bcl-2 family has been studied in various tissues including skin under normal as well as disease conditions. In this report, we investigated the expression of bad, the pro-apoptotic member of the BH3 subfamily, in normal and psoriatic epidermis, keratoacanthoma, and basal and squamous cell carcinomas. Normal and psoriatic epidermis showed accentuation of the staining in the lower suprabasal compartment. A weak, predominantly diffuse staining pattern was observed in the upper epidermis of psoriatic plaques. Keratoacanthoma showed strong but diffuse immunostaining for pro-apoptotic bad, however we found only weak bad expression in squamous cell carcinoma. Seven out of 15 basal cell carcinomas failed to express bad protein. There was no correlation between bad positivity and depth of tumour infiltration. Our observation suggests that the pro-apoptotic bad may function as one of regulators involved in the maintenance of epidermal homeostasis and this function could be altered depending on the disease state.

Schnitzler's syndrome versus adult onset Still's disease.

We report the case of a 50-year-old man with a 4-year history of high spiking fever accompanied by a widespread, urticarial, non-pruritic or only sometimes mildly pruritic eruption and arthralgia. He also had generalized lymphadenopathy, hepatosplenomegaly, and hyperosteoses of the lower lumbar spine. Laboratory examination revealed an elevated erythrocyte sedimentation rate, elevated white blood cell and platelet counts, hypoalbuminemia, and elevated serum IgM with IgM kappa monoclonal immunoglobulin. We diagnosed his condition as Schnitzler's syndrome, in contrast to the diagnosis of adult onset Still's disease, for which he had been initially followed up by his internist. We compare clinical and histopathological findings for both diseases and, as this patient meets two of the six existing diagnostic criteria for adult onset Still's disease, we propose that Schnitzler's syndrome is an important entity to be added to the list of differential diagnoses for adult onset Still's disease.

Expression of the bcl-2 homologue bax in normal human skin, psoriasis vulgaris and non-melanoma skin cancers.

Bax (bcl-2-associated X protein) is a recently identified member of the bcl-2 family and one of the principal inducers of apoptosis. We examined the distribution of bax protein in normal human skin and several skin diseases by immunohistochemistry. Bax immunoreactivity was present in normal epidermis and its appendages, with the suprabasal compartment being stained more strongly than basal keratinocytes. Bax immunostaining was also detected in the epidermis of psoriasis vulgaris and 5 keratoacanthomas examined. We could observe only weak bax immunoreactivity in 15 squamous cell carcinomas examined, with the exception of well-differentiated tumour islands in two tumours, which expressed immunostaining for bax comparable to that of normal suprabasal epidermis. Immunostaining for bax was negative in 12 out of 17 basal cell carcinomas and the remaining five tumours showed weak bax reactivity in tumour cells scattered within tumour masses and in palisading layers of some tumour formations. Western blot analysis confirmed the expression of bax protein in normal skin, psoriasis vulgaris and squamous cell carcinoma as well as the absence of bax in basal cell carcinoma. Our findings suggest that the loss of pro-apoptotic bax protein in basal cell carcinoma and its reduced expression in squamous cell carcinoma might be an important step in the development of these two skin cancers.

Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus hair cysts, and epidermoid and trichilemmal cysts.

We compared the patterns of keratin 10 (K10) and keratin 17 (K17) expression in epidermoid cysts, trichilemmal cysts, eruptive vellus hair cysts, and steatocystoma multiplex. Epidermoid cysts expressed K10 and eruptive vellus hair cysts expressed K17, whereas trichilemmal cysts and steatocystoma multiplex showed expression of both K10 and K17. Our findings support the opinion that eruptive vellus hair cysts, which stained negative for K10, and steatocystoma multiplex are distinct entities and not variants of one disorder.

Expression of bcl-2 antagonist bak in inflammatory and neoplastic skin diseases.

Bak (bcl-2 homologous antagonist/killer) is a proapoptotic member of the ever-expanding bcl-2 gene family, a recently described category of oncogenes that is critical for the regulation of programmed cell death. We investigated the expression of bak in several inflammatory and neoplastic skin diseases in comparison with normal skin. Immunohistochemical analysis revealed positive bak staining in epidermal keratinocytes of normal skin, with the granular layer being stained slightly more strongly than the basal and spinous layers, and in psoriasis vulgaris, lichen planus, actinic keratosis, keratoacanthoma and squamous cell carcinoma. We demonstrated the expression of bak in the follicular infundibulum in contrast to the outer root sheath of the lower follicle, which showed only negative to weak bak expression. Seventeen of 20 basal cell carcinomas examined showed negative immunostaining for bak, and the remaining three basal cell carcinomas showed only partial weak positivity, mainly in the palisading layers of some tumour formations. Immunoblot analysis using cultured normal human epidermal keratinocytes revealed the presence of bak protein in both undifferentiated and differentiated keratinocytes. The results of our study suggest that the loss of bak expression, in conjunction with the previously reported overexpression of bcl-2, might contribute to the pathogenesis of basal cell carcinoma.

Determination of some tricyclic neuroleptics by reversed-phase high-performance liquid chromatography with ultraviolet and polarographic detection.

The liquid chromatographic behaviour of various neuroleptics from the classes of tricyclic dibenzothiepins, -oxepins, -selenepins and similar substances was studied in an ion-pair reversed-phase system using a C4180 chemically bonded stationary phase and a methanol-water-acetic acid mobile phase. The best separation was attained with 70% methanol, 1.8% acetic acid and water, containing 0.005 M sodium pentanesulphonate, 1.2 X 10(-4) M EDTA and 0.5 g/l Na2SO4. For the detection, an ultraviolet spectrophotometric and a polarographic detector were connected in series. The detection was carried out at 254 nm and at a potential of a dropping mercury electrode of -1.0 V (vs. Ag/AgCl). The UV detector is universal, while the polarographic detector does not respond to compounds simultaneously containing two heteroatoms (O, S) in the central seven-membered ring. The detection limits are of the order of one to tens of nanograms, the polarographic detector being somewhat more sensitive for most of the compounds; the error of the determination is a few per cent. The method was applied to the determination of isofloxythepin and oxyprothepin in pharmaceutical preparations.