Temozolomide-induced desquamative skin rash in a patient with metastatic melanoma

Temozolomide is an oral alkylating agent used in the treatment of metastatic melanoma. Commonly reported adverse effects of the drug include nausea and vomiting, constipation, headache, and fatigue, as well as myelosuppression, which may be dose limiting. Few reports have described dermatologic adverse effects such as rash and pruritus, and, to our knowledge, none have discussed the seriousness or extensiveness of the rash. We describe a 37-year-old woman who was receiving temozolomide for treatment of metastatic melanoma. After 6 weeks of therapy, the patient developed an unexplained fever. The drug was discontinued, and the fever resolved within 2 days. Temozolomide was restarted 2 months later; the patient again developed a fever. This time the fever was accompanied by a diffuse erythematous skin rash that progressed to an extensive, full-body, desquamative skin rash. The rash was treated with moisturizing cream along with intravenous and topical corticosteroids and antibiotics. Due to the severity of the rash, temozolomide was permanently discontinued. Even after its discontinuation, the patient experienced the rash on a long-term basis, with periodic exacerbations. However, none were as severe as the first rash. The patient's metastatic disease remained stable for the next 2 years. According to the Naranjo adverse drug reaction probability scale, the likelihood that temozolomide was responsible for the adverse drug reaction of fever was probable (score of 6). Clinicians should be aware that an erythematous and exfoliative rash may be induced by temozolomide, and be familiar with the pharmacologic and supportive measures necessary for its treatment.     

Need for beta-blockade in hypertension reduced with long-term minoxidil.

Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients.     

Safety and tolerability of ingenol mebutate in the treatment of actinic keratosis

Introduction: Ingenol mebutate is a topical therapeutic agent for the treatment of actinic keratosis (AK). It has a novel mode of action and has shown comparable efficacy to other topical field therapies. This article summarizes and provides perspective on the safety profile of ingenol mebutate from clinical studies of this agent.

Areas covered: The unique mechanism of action of ingenol mebutate, the basis for a rapid clinical effect, is outlined. Safety and tolerability data, including mean composite local skin response (LSR) scores, type of LSR, and adverse events from a range of clinical studies both in healthy volunteers and patients with AK, are reviewed. The safety profile of ingenol mebutate is then compared with other agents used to treat AK lesions.

Expert opinion: Ingenol mebutate has a dosing period of 2 – 3 days, which is short compared with other field therapies, and there is no evidence of systemic absorption. The fact that most of the LSRs observed are mild to moderate in intensity and transient, with a majority resolved within 2 weeks, makes for a favorable safety profile. Ingenol mebutate enhances the armamentarium available to the dermatologist for the treatment of AK.     

Apparently normal phenytoin metabolism in a patient with phenytoin-induced rash and lymphadenopathy.

A 10-year old female on phenytoin therapy developed a rash and lymphadenopathy. H.p.l.c. assays of urinary metabolites indicated no differences in stereoselective metabolism of phenytoin to phenolic and dihydrodiol metabolites as compared with volunteers given the drug or with pediatric patients without adverse reactions. This suggests that no obvious difference in stereoselective metabolism of phenytoin to potentially toxic arene oxides exists between this patient and other patients on phenytoin. Our results are consistent with the hypothesis that differences in peripheral detoxication of phenytoin arene oxides and not differences in hepatic metabolism of phenytoin may be responsible for such adverse reactions.     

Treatment of severe hypertension with minoxidil: advantages and limitations.

Minoxidil, a new peripheral vasodilator, was used in the therapy of 26 hypertensives who were previously uncontrolled on conventional medications or who had dose-limiting side effects. Minoxidil provided (1) therapeutic advantages in all patients, regardless of the etiology of their hypertension, (2) no symptoms of orthostatic hypotension or sympathetic nervous system depression, (3) a simplification of medical regimens and perhaps costs, and (4) regression of impotence in four out of seven patients. The major limiting factors encountered were (1) fluid retention with the development of congestive heart failure in three patients, (2) pericardial effusion in three patients, and (3) hypertrichosis, which reduced its acceptability in female patients.     

光化性角化病病人皮肤组织 Toll样受体 7蛋白表达及其临床意义

目的探讨光化性角化病( AK)病人皮肤组织中 Toll样受体 7(TLR7)蛋白表达及其对 AK病人预后的预测效能。方法选取 2015年 1月至 2019年 1月四川大学华西医院收集的 134例 AK病人的皮肤蜡块标本作为观察组,选取同时期收集的 129例健康人员的皮肤蜡块标本作为对照组。采用免疫组化法测定两组皮肤组织的 TLR7蛋白表达情况,比较两组皮肤组织 TLR7蛋白表达水平。对观察组病人随访 3年,根据是否发展为皮肤鳞状细胞癌( cSCC)分为癌变组和非癌变组,对比癌变组与非癌变组皮肤组织中 TLR7蛋白表达水平,采用单因素分析和 logistic回归模型分析 AK病人进展为 cSCC的影响因素,采用受试者操作特征( ROC)曲线分析皮肤组织 TLR7蛋白表达水平对 AK病人发生 cSCC的预测效能。结果观察组皮肤组织中 TLR7蛋白表达水平高于对照组( 23.76±3.90比 4.95±0.64)(P<0.05); AK病人 cSCC发生率为 15.67%;癌变组与非癌变组皮肤病史、病程、病理类型比较差异无统计学意义( P>0.05),癌变组年龄高于非癌变组( P<0.05)男性、 Fitzpatrick皮肤分型为 Ⅰ/Ⅱ型的比例及皮肤组织 TLR7蛋白表达量高于非癌变组(P<0.05);高龄、男性、 Fitzpatrick皮肤分,型为 Ⅰ/Ⅱ型、皮肤组织 TLR7蛋白高表达均为 AK病人癌变发生的独立危险因素( P<0.05)且该模型拟合效果良好( P>0.05);皮肤组织 TLR7蛋白表达预测 AK病人进展为 cSCC的 ROC曲线的截断值 25.34,灵敏度 80.95%,,特异度 81.42%,ROC曲线下面积 0.81,95%CI:(0.74,0.88)。结论AK病人皮肤组织中 TLR7蛋白的表达量升高,且是 AK病人继发 cSCC的独立危险因素,对 AK病人的预后具有良好预测效能。     

甲苯磺酸索拉非尼致晚期肝癌患者高热伴皮疹

男性患者,56岁,因晚期原发性肝癌服用推荐剂量的索拉非尼(0.4 g,q12h)治疗。用药8 d后出现发热,体温最高至39.3℃。用药11 d开始出现皮疹,再次入院。入院后停用索拉非尼并给予抗过敏治疗,5 d后症状消退。随后给予低剂量索拉非尼(0.2 g,q12h),未出现发热及皮疹。5 d后索拉非尼加至0.4 g,q12h,治疗1 d后再次出现高热及新发皮疹。遂再次停用索拉非尼,高热及皮疹渐退。停用3 d后再次降低剂量至0.2 g,q12h。患者生命体征平稳、无畏寒、发热,无新发皮疹,病情稳定。该病例可为临床医生诊断索拉非尼引起的药物热及处理方法提供借鉴。     

Captopril combined with minoxidil,beta-blocker and furosemide in the treatment of refractory hypertension

Summary 14 Patients with refractory hypertension did not respond either to captopril, an angiotensin II converting enzyme inhibitor, combined with a diuretic, a beta-blocker and hydralazine or minoxidil, a potent vasodilator, but they did respond to the combination of captopril, minoxidil, furosemide and a beta-blocker. There were no disturbing side effects from this combination. There may be a synergistic effect between captopril and minoxidil in the treatment of refractory hypertension. The combination is an interesting and novel method of treating patients with refractory hypertension.     

Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response

Bevacizumab (Avastin) in combination with intravenous 5-fluorouracil-based chemotherapy as first-line as well as second-line treatment of metastatic colorectal cancer improves survival. Although skin rash (type unspecified) has been described in some patients following infusion of bevacizumab, it is not a common toxicity of bevacizumab, while acneiform rash occurs in more than 90% of patients who receive cetuximab (Erbitux), the severity of which appears to be predictive of response. We report a patient with colorectal cancer who developed a rash secondary to bevacizumab that correlated with response. A 40-year-old patient with stage IV colorectal cancer received FOLFOX-4 and bevacizumab, which he tolerated very well except for a skin rash related to bevacizumab. The rash cleared every time bevacizumab was eliminated from the chemotherapy regimen. When use of bevacizumab was resumed, similar rash reappeared. Therefore, we believe that this observation of the rash emergence was linked to bevacizumab administration. The most common toxicities associated with bevacizumab include hypertension, hemorrhage, gastrointestinal perforation, arterial thromboembolism, wound healing and proteinuria. Exfoliative dermatitis and a nonspecific rash have been reported with bevacizumab. This case report, we believe, is the first report of a possible correlation between a rash and a positive drug response associated with bevacizumab, and may initiate further investigation of similar observation.     

Cellulitis as a postprocedural complication of topical 5-aminolevulinic acid photodynamic therapy in the treatment of actinic keratosis

BACKGROUND: Actinic keratoses (AKs) are a common premalignant tumor of the skin. Several treatment modalities exist for broad-area therapy. Photodynamic therapy (PDT) is one such treatment modality. Disruption of squamous epithelium locally compromises the normal physical barrier of the skin, potentially allowing bacteria penetration into the dermis. This may occur subsequent to PDT, resulting in cellulitis and its sequelae. Undiagnosed and untreated this can prolong recovery times and increase patient discomfort. OBJECTIVE: We report 4 cases of cellulitis that developed after treatment of AKs with PDT. These cases developed 1 to 4 days after PDT. METHODS: Standard short-contact 2-hour incubation is performed on patients receiving treatment on the face or scalp. Patients are contacted by telephone on day 1 and day 3 postprocedure. Patients are asked to call immediately if they experience no resolution of discomfort or an abrupt increase in pain in the days following treatment. Those patients reporting an increase in pain and discomfort on either of these days are asked to come to the office for examination. A culture and sensitivity is performed on those presenting with cellulitis clinically and empiric antibiotic therapy is initiated. Antibiotic therapy is adjusted, if necessary, based on the culture and sensitivity report. RESULTS: All cases of cellulitis presented with an increase in pain and burning as the primary symptom between day 1 and 4 following PDT. The appearance of impetiginized areas or pustules was clearly evident in 2 out of the 4 patients. A culture and sensitivity confirmed the growth of staphylococcus aureus in all 4 patients. CONCLUSION: Cellulitis should be considered as a possible complication in patients reporting an abrupt increase in pain or those who do not experience a gradual resolution of pain and discomfort following PDT.     

Prospective, case-based assessment of sequential therapy with topical Fluorouracil cream 0.5% and ALA-PDT for the treatment of actinic keratosis

The sequential use of topical therapies and short-incubation photodynamic therapy for actinic keratosis (AK) has not been extensively studied. The author reports on treatment with sequential 5-fluorouracil (5-FU) cream 0.5% and 5-aminolevulinic acid?photodynamic therapy (ALA-PDT) in three older men with photodamaged skin and a history of AK. These findings suggest that this combination therapy, when compared with short-contact (1 hour) ALA-PDT alone, is more effective, minimizes the recurrence of areas of field cancerization and improves the appearance of the skin. The use of 5-FU cream 0.5% before and after photodynamic therapy is effective in revealing the presence of both clinical and subclinical AK lesions.     

1例男性青年难治性高血压的药学监护分析

临床药师通过参与临床药物治疗,进行药学监护,协助临床医生进行1例男性青年难治性高血压的治疗。药师参与患者初始治疗方案选择,并根据相应指南和共识参与治疗药物调整并开展安全性、有效性、依从性药学监护及患者用药教育,参与患者在院期间多种药物的调整,血压由入院165/98 mmHg降至出院143/84 mmHg(1mmHg=0.133 kPa),心率入院80次/分至出院63次/分,尿酸由入院594μmol·L~(-1)降至出院510μmol·L~(-1),血肌酐入院224μmol·L~(-1)至出院216μmol·L~(-1),血钾在院期间无较大波动。患者未出现因血压改变导致头晕跌倒等恶性事件,并开始记录血压日志,治疗依从性良好。临床药师与医师在沟通中学习心内科医师治疗难治性高血压的经验知识,加深对难治性高血压诊治的认识,关注细节、对比联系,这也是临床药师开展药学监护工作的出发点。     

Treatment options for a patient experiencing pruritic rash associated with transdermal testosterone: a review of the literature.

A 22-year-old man with hypogonadotropic hypogonadism was receiving monthly intramuscular injections of testosterone replacement therapy. The patient refused to self-administer the injections because of discomfort, so the therapy was switched to testosterone patches. He experienced a pruritic, macular, erythematous rash underneath the reservoir area of two different transdermal formulations, which did not improve after pretreatment with topical corticosteroids. Eventually, he tolerated application of a testosterone gel and his serum testosterone levels returned to normal after 1 month of therapy. Commercially available and investigational testosterone products and therapeutic monitoring guidelines for androgen replacement are reviewed.     

高血压患者服用比索洛尔治疗心悸致剧烈咳嗽

1例52岁男性高血压患者,口服缬沙坦80 mg/d治疗6年余.因冠状动脉粥样硬化性心脏病行冠状动脉支架植入术.术后加服氯吡格雷片75 mg/d、阿司匹林肠溶片100 mg/d、单硝酸异山梨酯缓释片40 mg/d及阿托伐他汀钙片10 mg/d.约1个月后因心悸又加服比索洛尔片5 mg/d.治疗3 d后,患者出现刺激性干咳.血常规、胸部X线片及超声心动图检查未见异常.给予对症治疗无明显效果.停用比索洛尔,3 d后咳嗽好转.5个月后,患者因心悸再次服用比索洛尔,剧烈咳嗽再次出现,用可待因治疗无效,停服比索洛尔1周后症状消失.