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PubMed2005

Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals.

BACKGROUND: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established. OBJECTIVES: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals. METHODS: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks). RESULTS: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11-29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure. CONCLUSIONS: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.

Administration, Cutaneous↗
PubMed1998

Hand-foot syndrome following prolonged infusion of high doses of vinorelbine.

BACKGROUND: The authors reviewed the incidence of toxic skin reactions in patients with metastatic breast carcinoma (MBC) treated with vinorelbine as a continuous infusion. METHODS: A Phase I/II protocol was designed in which vinorelbine was given as an 8-mg intravenous bolus followed by a 96-hour CI of 7-14 mg/m2/day. Sixty patients were enrolled in the study: all had MBC and had received prior chemotherapy, and they had no known dermatologic disorder. RESULTS: Hand-foot syndrome (HFS) developed in 4 of the 60 patients. Patient 1 started with vinorelbine at 12 mg/m2/day. She developed typical HFS. In the second course, her dose was decreased to 11 mg/m2/day, but again she experienced HFS. In the third course, dexamethasone was added to the regimen, and no HFS was observed in the remaining six courses. Patient 2 started with a dose of 9 mg/m2/ day. She received four courses without complications; but when the vinorelbine dose was escalated to 10 mg/m2/day, HFS developed. Patient 3 started with a vinorelbine dose of 14 mg/m2/day. She developed mucositis during the first two courses and HFS during the third. Patient 4 received vinorelbine at a dose of 13 mg/m2/day and developed significant HFS. All patients had complete dermatologic recovery. No toxic skin reactions were observed in 14 patients receiving vinorelbine doses of <10 mg/m2/day, whereas 4 of 46 treated at 10-14 mg/m2/day developed HFS, suggesting a relationship of dose to HFS occurrence. CONCLUSIONS: Longer infusions of vinorelbine are occasionally associated with HFS. The pathophysiology is not completely clear, but a relationship of HFS occurrence to dose is suggested. Steroids were effective as prophylaxis in one patient.

Adult↗
PubMed1999

Recalcitrant viral warts treated by diphencyprone immunotherapy.

Recalcitrant viral warts are a troublesome therapeutic problem. Immunotherapy with the universal allergic contact sensitizer diphencyprone (DCP) has been used successfully in such cases. We have reviewed our experience of the use of DCP in the treatment of resistant hand and foot warts during an 8-year period. Sixty patients were sensitized to DCP during this time; the median duration of warts was 3 years. Twelve patients defaulted from treatment. Of the remaining 48 individuals, 42 (88%) cleared of all warts. The median number of treatments to clear was five (range one to 22) and the median time to clear was 5 months (range 0.5-14). Adverse effects occurred in 27 of 48 patients (56%), most commonly painful local blistering (n = 11), blistering at the sensitization site (n = 9), pompholyx-like reactions (n = 7) and eczematous eruptions (n = 4). Three of those who defaulted did so due to side-effects, one became pregnant and eight dropped out for unknown reasons. Three of the 48 patients who cleared or had at least six treatments also discontinued DCP therapy due to side-effects, but most tolerated treatment well. Twenty-five patients were followed up for periods of 1 month to 8 years (median 2 years) and none had a recurrence. DCP immunotherapy is an effective option for the treatment of recalcitrant viral warts but patients must be motivated to attend for sequential applications and must be warned about potential uncomfortable side-effects.

Adolescent↗
PubMed1997

Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion.

The aim of this study was to examine in detail the incidence and severity of hand-foot syndrome in advanced colorectal cancer patients receiving 5-fluorouracil (5-FU) and leucovorin (L-LV) chemotherapy. 70 advanced colorectal cancer patients (pts) were given weekly 24 h continuous 5-FU (2600 mg/m2) infusion plus L-LV (100 mg/m2 i.v., 50 mg orally). The toxicity, in particular HFS, was analysed, correlated to the main pts characteristics and compared to the other observed side-effects. HFS occurred in 36/70 pts (51%): grade 1 in 16 pts, grade 2 in 16 pts, grade 3 in 3 pts and grade 4 in 1 pt. It occurred after a median number of nine courses. In one case, chemotherapy was interrupted for this toxicity, and in another 5 pts drug reduction and/or treatment delay were undertaken. Changes in the therapeutic programme because of diarrhoea or mucositis were more frequent, even though these toxicities were generally mild in our series of pts. HFS was significantly correlated to previous exposure to chemotherapy (P = 0.00003). HFS was a frequent side-effect of high-dose, short-term continuous 5-FU infusion, but the impact on quality of life of pts and on the correct delivery of the planned chemotherapy was limited.

Adult↗
PubMed1991

Bazex syndrome (acrokeratosis paraneoplastica). An analytic review.

Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions.

Carcinoma, Squamous Cell↗
PubMed1989

Demonstration of in vitro synthesis of human papilloma viral proteins from hand and foot warts.

HPV particles purified from [35S]-methionine labeled and unlabeled halves of single hand and foot warts have been fractionated into empty, light full, and heavy full particles by buoyant density gradient centrifugation, and their proteins analyzed by two-dimensional gel electrophoresis (IEF and NEPHGE) and visualized by either fluorography or silver staining. The L1 coat protein (54 Kd) was found in trace amounts in unmodified and slightly modified forms in the labeled empty and light full particles but could not be detected in the labeled heavy particles. L1 appeared to exist in the three unlabeled particle types in differentially modified forms. A putative L2 protein was also found to be modified (74-80 Kd) and was found preferentially in the unlabeled heavy full particles. The commercial cross-reactive BPV antibody recognized a labeled 58-Kd protein found predominantly in the empty and light full particles and a pair of proteins (41-42 Kd) found unlabeled in the heavy full particles. Besides L1, there were several other proteins (IEF 40 Kd; NEPHGE 42, 38, and 36 Kd) which were detected labeled in the empty particles and in increasing unlabeled amounts in the light full and heavy full particles. Four proteins (IEF 66, 13 and 11 Kd, and NEPHGE 9 Kd) were found exclusively in the full particles and may be involved in packing the viral genome. These observations suggest that a virus particle assembly pathway exists from the empty particles, via the light full, to the mature heavy full particles.

Bovine papillomavirus 1↗
PubMed2004

Lack of contribution of dihydrofluorouracil and alpha-fluoro-beta-alanine to the cytotoxicity of 5'-deoxy-5-fluorouridine on human keratinocytes.

Capecitabine (Xeloda) is a very active oral fluoropyrimidine (colon and breast cancers) whose clinical use is complicated by the presence of hand-foot syndrome (HFS). This cutaneous toxicity is less frequently encountered with other oral fluoropyrimidines containing a dihydropyrimidine dehydrogenase (DPD) inhibitor. The HFS is thus attributed to the presence of the main 5-fluorouracil (5-FU) metabolites, dihydrofluorouracil (5-FUH2) and alpha-fluoro-beta-alanine (FBAL), but without strong pharmacological arguments. The aim of the present study was to closely examine this latter hypothesis. Capecitabine generates 5'-deoxyflourouridine (5'-DFUR) which is transformed into 5-FU at the cellular target site through the intermediary of thymidine phosphorylase (TP). The cytotoxic effects (MTT test, 4-day exposure) of 5'-DFUR, 5-FU, 5-FUH2 and FBAL were tested against the spontaneously immortalized human keratinocyte cell line (HaCaT) and the human cancer colon cell line WiDr as a control. Mean IC50s on HaCaT and WiDr were, respectively, 1.3 and 10 microM for 5'-DFUR, 0.2 and 3.3 microM for 5-FU, 13.4 and 560 microM for 5-FUH2, and greater than 650 and 6500 microM for FBAL. The respective 5'-DFUR IC50s values were not different when cells were exposed to 5'-DFUR alone or in combination with 5-FU, 5-FUH2 and FBAL in both cell lines, the relative proportion of each drug reflecting known pharmacokinetic data for capecitabine (5'-DFUR 12.4%, 5-FUH2 6.4%, 5-FU 1.2% and FBAL 80%). This latter finding demonstrates the relative lack of significant cytotoxic activity of 5-FUH2 and FBAL on human keratinocytes. TP activity was particularly high in HaCaT cells and DPD activity was very low in both cell lines. These data strongly suggest that the presence of 5-FU metabolites does not play a major role in the HFS generated by capecitabine and that it can probably be attributed to particularly high TP activity in keratinocytes. This observation may have important clinical consequences such as a possible local pharmacological inhibition of TP for controlling HFS.

Antineoplastic Agents↗
PubMed2004

Oral dexamethasone attenuates Doxil-induced palmar-plantar erythrodysesthesias in patients with recurrent gynecologic malignancies.

OBJECTIVE: The aim of this study is to evaluate the effect of oral dexamethasone in attenuating palmar-plantar erythrodysesthesias (PPE) in Doxil-treated patients for gynecologic malignancies. METHODS: An IRB-approved prospective case study was conducted in patients with recurrent gynecologic malignancies who were treated with Doxil (50 mg/m(2)) on a 28-day cycle. Patients experiencing grades II-IV PPE were delayed until resolution then retreated without dose reduction and with a tapering oral dexamethasone regimen (8 mg BID days -1 to 4; 4 mg BID day 5; 4 mg day 6). Standard treatment for grades II-IV PPE in those not receiving dexamethasone was weekly dose delay until resolution of symptoms up to 2 weeks. If resolution occurred within 3 weeks of delay, a 25% dose reduction was made. Persistent grades III/IV PPE resulted in withdrawal of Doxil. RESULTS: Twenty-three patients (ovarian-16, uterine-7) were treated between January 1998 and December 2000. The median number of cycles administered was 5 (range 1-20). Nine patients (39%) developed grades II-IV PPE. All nine patients received more than five cycles of Doxil. The median time to PPE was 3 cycles (range 2-5). Six out of nine PPE patients received scheduled dose dexamethasone. All six had complete or near complete resolution of PPE and all continued treatment without subsequent dose modification. All three of the nine PPE patients not receiving dexamethasone required treatment delays and were dose reduced. CONCLUSION: Oral dexamethasone is effective in attenuating or eliminating Doxil-induced PPE. The use of the dexamethasone regimen prevents treatment delay and dose reduction.

Administration, Oral↗
PubMed2003

Specific site involvement in fixed drug eruption.

A total of 105 patients with established fixed drug eruption (FDE) by oral provocation were evaluated with regard to a drug-related site involvement. Cotrimoxazole was the leading causative agent (63.8%), followed by naproxen sodium (23.8%), dipyrone (5.7%), oxicams (4.8%) and other rare causes (1.9%). Cotrimoxazole most frequently induced lesions on genital mucosa; naproxen and oxicams on lips; and dipyrone on trunk and extremities. Isolated FDE on male genitalia (n = 16) was exclusively because of cotrimoxazole. A highly significant association could be established between naproxen and FDE on lips (chi-square = 28.3; corrected P =.000002). As this study represents the largest series of patients with naproxen-induced FDE, we would suggest that naproxen should be considered as an important potential cause of FDE on lips.

Adolescent↗
PubMed2005

Onychomycosis caused by Fusarium proliferatum.

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.

Antifungal Agents↗
PubMed1996

Contact dermatitis from fatty alcohols.

The aim of this study was to investigate the frequency of sensitization to fatty alcohols in a group of patients with suspected cosmetic or medicament contact dermatitis. From May 1992 to September 1995, we patch tested a series of 5 fatty alcohols on 146 patients. These included 108 females and 38 males aged from 13 to 72 years (mean age 42.5). These patients, who had previously been tested with the GIRDCA standard series, were selected because their clinical lesions or histories indicated topical preparations as the possible source of their contact dermatitis. High-grade fatty alcohols (> 99% pure) were used for testing. 34 patients (23.2%), 25 female and 9 male aged from 14 to 72 years, showed a positive patch test to fatty alcohols, 33 of them to oleyl alcohol. A total of 39 reactions were detected with 5 patients showing more than 1 positive reaction. Our results show that sensitization to oleyl alcohol is not rare in patients with contact dermatitis due to cosmetics or topical medicaments.

Adolescent↗