Hydrochlorothiazide/Lisinopril

An active 62-year-old man with noninsulin-dependent diabetes and chronic tinea pedis and tinea unguium developed a painless neurotrophic foot ulcer. His medical history was significant for mild hypercholesterolemia, chronic obstructive pulmonary disease, and long-term tobacco and alcohol use. Oral medications were Glyburide, Glucophage, Zestoretic, gemfibrozil, and aspirin, all of which had been administered daily for at least 8 months. There was no personal or family history of skin disease. After the ulcer failed to respond to conventional therapy, including wound care, debridement, and oral antibiotics, oral terbinafine was prescribed, 250 mg/day, for dermatophytosis-impaired wound healing. After 44 days of terbinafine therapy, the patient developed a generalized, erythematous, maculopapular, pruritic eruption accompanied by fatigue and chills. He denied cough, arthralgias, dizziness, hematuria, or exposure to anyone ill. Despite instructions to stop taking the medication, the patient erroneously continued to take terbinafine. One week later, he was referred to our institution. Physical examination revealed a nontoxic appearing middle-aged man with diffuse, confluent, erythematous plaques studded with pustules, lakes of pus, and crusted erosions and a fever of 38.9 °C ( Figs 1 and 2). Palms, soles, and mucous membranes were unaffected, and the groin was relatively spared. Toenails exhibited yellow–white discoloration, subungual debris, and onychauxis. Fingernails were normal. Lymphadenopathy was absent. A 1.3 cm by 1.7 cm superficial, painless ulcer without significant undermining was present on the left sole over the first metatarsophalangeal joint. There was decreased sensation from the toes to the midleg. Pedal pulses were palpable. Figure 1. Extensive pustular eruption of acute onset involving the trunk and extremities Download figure to PowerPoint Figure 2. Erythematous plaques, pustules, lakes of pus, and crusted erosions Download figure to PowerPoint Laboratory analyses revealed elevated white blood cell count (10.7 × 103 μL) with 11% eosinophils. Electrolytes, renal, thyroid, and liver function tests, urinalysis, and sedimentation rate were normal. A skin biopsy specimen showed an intraepidermal, spongiotic, vesiculopustular dermatitis with a superficial, perivascular, mixed inflammatory cell infiltrate of lymphocytes, neutrophils, and scattered eosinophils ( Figs 3 and 4). A periodic acid–Schiff stain was negative for fungi. Figure 3. Vesiculopustular dermatitis with diffuse superficial perivascular infiltrate (original magnification, ×10) Download figure to PowerPoint Figure 4. Subcorneal neutrophilic pustule, perivascular infiltrate of mononuclear cells, neutrophils, and occasional eosinophils (original magnification, ×40) Download figure to PowerPoint Terbinafine was stopped, but all other medications were continued. Hydrotherapy, twice-daily triamcinolone ointment, and a prednisone taper from 60 mg to 0 mg over 3 weeks were initiated. In 4 days, there was complete resolution of the fever and pustulosis and a significant reduction of the erythema. At 40 days, mildly pruritic, erythematous plaques persisted on the trunk and extremities. The temporal relationship strongly suggested terbinafine as the inciting agent in this patient. Oral provocation test was not performed due to unacceptable patient risk.

The objective of this study was to compare the effectiveness of three treatment methods available for treatment of previously medicated patients with mild to moderate hypertension. The comparison was made between adjusting or increasing previous medication and switching the previous drug treatment to lisinopril (CAS 76547-98-3) or lisinopril hydrochlorothiazide (CAS 58-93-5) therapy and in both of these treatment groups the effect of additional intensified health education was tested. An open, randomised, controlled multi-centre study lasting 36 weeks involving 189 doctors and 69 nurses was carried out in 155 centres of primary health care and occupational health care system in Finland. The study population consisted of 1156 patients, age 30-70 years, (mean DBP 95-115 mmHg in the last three to five measurements during follow-up). The number of patients achieving target pressure (DBP < 90 mmHg) at the end of the study, defined daily doses (DDD) of antihypertensive drugs and side-effects in different treatment groups were regarded as the main outcome measures of the study. After exclusions and drop-outs the final analysis was carried out with 900 patients, 419 women (46.6%) and 481 men (53.4%). Patients receiving lisinopril treatment achieved target pressure significantly more often (p < 0.001) than those continuing their previous or adjusted medication at 36 weeks (59.2 and 55.5% vs 40.3 and 42.7%). Only a small additional but statistically non-significant blood pressure lowering effect was achieved with intensified non-pharmacological treatment at weeks 12 and 24, but this difference had disappeared at week 36. The mean DDDs of different antihypertensive drugs did not differ between groups except for female patients on previous or adjusted medication not receiving health education, the mean DDD being significantly (p < 0.05) higher at weeks 24 and 36 in this group. The profile of adverse effects at the end of the study clearly favoured patients on lisinopril treatment except for cough which was reported in 18% of patients vs 10% in the control groups. 81 patients on lisinopril treatment were withdrawn from the study because of cough. The results showed that hypertensive patients with poor treatment control benefit from all three approaches. A greater proportion of patients on lisinopril treatment achieved target pressure and also experienced fewer side effects than those continuing on adjusted previous medication. Intensified personal health education given once a month during six months had only a small additional beneficial effect on reaching the target pressure and this effect was lost in three months after the health education period.