Dupuytren, Ledderhose, and Peyronie Diseases After Primidone Use For Essential Tremor.

INTRODUCTION: Dupuytren, Ledderhose, and Peyronie diseases are chronic fibrotic conditions related to progressive fibrosis of the palmar fascia, plantar fascia, and tunica albuginea, respectively. These conditions have been associated with antiepileptic drug use, mainly phenobarbital and primidone. CASE REPORT: A 71-year-old man developed simultaneous Dupuytren, Ledderhose, and Peyronie diseases after primidone use for essential tremor. CONCLUSIONS: There are a few reports associating barbiturate use to connective tissue disorders, and some suggest that drug withdrawal may result in a better prognosis. Therefore, physicians must be aware of such adverse events when caring for patients on long-term barbiturate use.

Peyronie's disease and Dupuytren's contracture secondary to topical timolol.

INTRODUCTION: Topical beta-blockers are a proven and safe medication used in the treatment of glaucoma and ocular hypertension. Local and systemic side effects are, however, well documented. Systemic side effects can include severe cardio-respiratory impairment, endocrine dysfunction, as well as headache and hyper-somnolence. Disorders involving fibrosis such as Peyronie's disease, Dupuytren's contracture, and retroperitoneal fibrosis are rarely described in the literature. CASE REPORT: We describe a case of a 55-year-old male patient undergoing treatment for ocular hypertension with topical timolol 0.25% to both eyes, who subsequently developed both Peyronie's disease and Dupuytren's contracture. To our knowledge, this is the first case of Dupuytren's contracture secondary to the use of topical timolol. CONCLUSIONS: Whilst uncommon, beta-blockers are known to be associated with such fibrotic conditions and have been reported with the use of topical timolol. This case serves to increase the current understanding of this association.

Vemurafenib-associated Dupuytren- and Ledderhose palmoplantar fibromatosis in metastatic melanoma patients.

BACKGROUND: The BRAF-inhibitor vemurafenib, used in patients with metastatic melanoma, induces multiple cutaneous side-effects. OBJECTIVE: The aim of this work was to evaluate the development of palmoplantar fibromatosis in a population of patients treated with the BRAF inhibitor vemurafenib. METHODS: Between April 2011 and February 2013, we initiated a treatment with vemurafenib in 53 patients with an unresectable stage IIIC or stage IV melanoma. The patients were followed-up on a regular base to monitor possible side-effects. RESULTS: A plantar or palmar fibromatosis was observed in five of 53 patients treated with vemurafenib. In four of these patients other risk factors for the development of palmoplantar fibromatosis were absent. CONCLUSION: The BRAF-inhibitor vemurafenib might induce palmoplantar fibromatosis.

Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report.

INTRODUCTION: Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation. CASE PRESENTATION: A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960 mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent. CONCLUSIONS: Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures.

Dupuytren's contracture as result of prolonged administration of phenobarbital.

Dupuytren's disease is a fibroproliferative condition involving the superficial palmar fascia, leading to a progressive and irreversible flexion of the fingers. In literature, there are different opinions regarding the phenobarbital, a common antiepileptic drug, and its effective role in the genesis and development of Dupuytren's disease. In this retrospective investigation the association between phenobarbital and Dupuytren's contracture is discussed. Three patients in treatment with phenobarbital who had no others significant risk factors for Dupuytren's contracture were included in this study. The disease occurred after one to four years of drug therapy, at dosage of 100 mg/day. After surgery, Dupuytren's disease showed different evolutions in relation to dosage and type of antiepileptic drug used. Phenobarbital causes a dose and time-dipendent profibrotic effect. A clinical regression was observed when phenobarbital was substituted by carbamazepine, maintaining the same dosage (100 mg/day). This data confirms that not all the antiepileptic drugs are implicated in palmar fibrosis, and suggests that, according to the efficacy and adverse effects, the administration of benzodiazepine reduces the risk of Dupuytren's recurrence.

Rheumatological complications associated with the use of indinavir and other protease inhibitors.

Several cases are reported of rheumatological pathology (temporomandibular dysfunction, frozen shoulder, Dupuytren's disease, and tendinitis) most probably related to the intake of indinavir in HIV positive patients. A survey using an anonymous questionnaire of 878 people with HIV infection treated with antiretroviral drugs suggests that other protease inhibitors may also cause arthralgia.

[Dupuytren's and Ledderhose's diseases associated with chronic use of anticonvulsants. Case report]. / Doenças de Dupuytren e de Ledderhose associadas ao uso crônico de anticonvulsivantes. Relato de caso.

We present the case of a patient that after chronic use of anticonvulsant drugs without proven epilepsy, developed Dupuytren's and Ledderhose's diseases. We discuss the most frequent predisposing factors, and their relationship with chronic use of anticonvulsants, particularly phenobarbitone.

Dupuytren's disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor.

In a series of 12 patients with inoperable gastric carcinoma who had treatment with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than one month, six developed a frozen shoulder or a condition resembling Dupuytren's disease. This suggests that the matrix metalloproteinases, a family of naturally occurring proteinases, may be involved in the pathogenesis of these two conditions. Our observation opens avenues for further research which could lead to local or systemic therapeutic interventions for frozen shoulder and Dupuytren's disease.

Reflex sympathetic dystrophy associated with antiepileptic drugs.

Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEDs. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond to a change in AEDs, but all improved with a course of prednisone. One patient with phenobarbital (PB)-associated RSDS relapsed on inadvertent rechallenge with secobarbital. A review of the literature showed that several other fibrosing disorders are associated with AED administration, including Dupuytren's contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease. RSD associated with AEDs is important to recognize because it may result in permanent disability if treatment is delayed.

Dupuytren's and epilepsy revisited.

The incidence of Dupuytren's disease amongst the residents of two epileptic centres was found to be 12.0% in one and 38.1% in the other. The overall incidence at the second was significantly higher than a control population (16.0%) and this difference was particularly apparent in patients over 50 years old. The distribution of the Dupuytren's disease was found to be very similar to that of non-epileptic patients. At both centres, the disease process was more severe, with an increased incidence of contractures. Drug therapy was not clearly implicated in the aetiology of this condition.

[Side effects of antiepileptic therapy. Study of 197 cases]. / Les effets secondaires des traitements antiépileptiques. Etude de 197 cas.

A study of 197 epileptic outpatients consecutively observed by one Neurologist allowed a prospective study of the side effects of antiepileptic drugs. This study shows essentially that a clinical improvement comparable to that generally reported can be obtained with side effects limited in their number and intensity. The main principle is the routine search of these effects which are not always spontaneously mentioned by the patients, especially intellectual slowness and loss of sexual activity. The detection of the side effects through history and physical examination is far more fruitful than are plasma concentrations of drugs which can be doubly misleading: some plasma concentrations lower than recognized therapeutical levels are efficient however while others are higher and nevertheless necessary and well tolerated. Among the side effects specific to certain antiepileptic drugs, shoulder-hand syndrome due to phenobarbital was noted in 10 per cent of the cases. Furthermore, the frequency of scapulo-humeral periarthritis was significantly higher in the epileptic group than in the controls. Dupuytren's disease was less frequent (8 per cent) and the difference with the controls was not significant. Among the non-specific side effects, nystagmus is a somewhat useful sign in treatments by phenytoin but as with drugs dosages, it must be weighed within the whole clinical picture.

[Dupuytren contracture in Mosel wine dressers with arsenic-induced aftereffect damage]. / Dupuytren'sche Kontrakturen bei Moselwinzern mit Arsenspätfolgeschädigung.

Between 1972 and 1981 a total of 121 male and female wine-dressers with late after-effects from arsenic were medically examined and treated. Skin and liver were examined regularly every 3 months. With advancing years an increase in typically arsenic melanosis, precancerous, carcinomas and hyperkeratosis in palmae and plantae was observed. A significant increase in Dupuytren's contracture was found in the age groups between 50 and 80 with a growing progression of typically arsenic horned pearls on the palms of the hands and soles of the feet. The typically arsenic horned pearls and arsenical keratosis occurred most frequently in the Dupuytrenical changes of the skin. The liver parameters showed no pathological results such as cirrhosis of the liver as compared with the other patients.

[Dupuytren's contracture and palmar erythema in alcoholic cirrhosis]. / Maladie de Dupuytren et érythrose palmaire au cours des cirrhoses éthyliques

Three comparable groups were studied : 100 patients with alcoholic cirrhosis, 100 alcoholics without cirrhosis, and 100 subjects without either alcoholism or cirrhosis. Dupuytren's contracture was noted in 43% of cases in group I, 34% in group 2, and in 14% of group 3. There was no parallel between the frequency of Dupuytren's contracture and the severity of the liver involvement. Palmar erythema was noted in 34% of cases of group 1, 23% of cases of group 2, 12% of cases of group 3. Dupuytren's contracture has a genetic background, but its clinical expression is facilitated by metabolic causes, the most frequent being chronic alcoholism. Palmar erythema appears to be a sign of severe liver disease.