Peripheral sensory neuropathy associated with short-term oral acitretin therapy

A 57-year-old female patient with widespread chronic plaque psoriasis and a 32-year-old male patient with severe oral lichen planus are reported, who developed sensory symptoms in the extremities 3 and 4 months after the onset of oral acitretin therapy, respectively. Both patients showed clinical and electrophysiological evidence of a sensory peripheral neuropathy, which completely resolved 2 and 2.5 years after discontinuation of oral acitretin administration, respectively.     

Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin and adipose tissue.

The purpose of the present study was to determine the concentrations of acitretin and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months. In addition, endogenous concentrations of vitamin A were monitored. Blood samples and biopsies from normal appearing skin were obtained prior to therapy, after 1 and 6 months of treatment and finally 1 month after cessation of therapy. Using a highly sensitive liquid chromatography method concentrations of synthetic retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a significant correlation between the individual plasma trough value and the epidermal concentration of acitretin after 1 month of therapy. The acitretin concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1 and 6 months of therapy were similar (177 and 227 ng/g, respectively). After stopping therapy the acitretin level was below the detection limit in both epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3 of the patients were negative for acitretin in subcutis biopsies obtained 1 month after stopping therapy. The occurrence of a presumed tissue contaminator with characteristics similar to 13-cis acitretin prevented quantitation of this metabolite in many subcutis samples. The epidermal, subcutis and serum composition of retinol and 3,4-didehydroretinol remained unchanged during therapy, indicating no or only minimal interaction between acitretin and endogenous vitamin A metabolism.     

Effects of oral isotretinoin therapy on peripheral nerve functions: a preliminary study

Accumulating evidence over the past decade indicates that synthetic retinoids may be capable of affecting both growth and differentiation of nervous tissue. Our aim was to substantiate possible side-effects of oral isotretinoin therapy on peripheral nerve functions, both neurologically and neurophysiologically. We performed neurological examination and electroneuromyographic studies on 18 patients with various skin diseases before, at the third month, and at the end of isotretinoin treatment. Abnormal neurophysiological findings in this study point towards a typical distal, length-dependent and predominantly sensory polyneuropathy. Clinicians should be aware of possible neurological sensorial symptoms during isotretinoin therapy. In our opinion, electroneuromyographic investigation should be performed on all patients reporting symptoms (e.g. paresthesia, numbness, sensory loss) before and during oral isotretinoin treatment. The precise clinical significance of the isotretinoin-induced neurophysiological alterations reported here remains to be determined in further studies.     

Acitretin is converted to etretinate only during concomitant alcohol intake

BACKGROUND: Acitretin has replaced etretinate in the treatment of various disorders of keratinization due to a considerably shorter terminal half-life. Possible esterification of acitretin to etretinate in the presence of ethanol has been reported. OBJECTIVES: To determine the plasma concentrations of etretinate as a metabolite in patients with various disorders of keratinization after multiple acitretin dosing, and to assess the influence of alcohol consumption using a questionnaire. In addition, to study the influence of alcohol consumption on the risk of metabolic formation of etretinate. PATIENTS/METHODS: Eighty-six acitretin (Neotigason(R), Roche)-treated outpatients from three centres provided pre-dose (trough) samples for determining plasma concentrations of acitretin and its metabolites 13-cis-acitretin and etretinate. Patients received acitretin doses of between 0.1 and 1.3 mg kg-1 daily. The concentrations of etretinate, acitretin and 13-cis-acitretin were determined by reverse-phase high-performance liquid chromatography. RESULTS: Of the 86 patients, 30 had detectable plasma etretinate levels. No etretinate was found in 20 patients who reported that they never drank alcohol, while etretinate was found in all 16 patients with an average weekly alcohol consumption of > 200 g ethanol, corresponding to about 15 U (1 U equals half a pint of standard beer or a wine glass of non-fortified wine). Etretinate was detected in 14 of 50 patients with a moderate weekly alcohol intake of up to 200 g ethanol. A trend linking higher alcohol intake with both higher risk of etretinate formation and higher etretinate levels was observed. The study also revealed that the ethylesterification only relates to acitretin (13-trans-) and not to the main metabolite 13-cis-acitretin, although the latter compound showed higher plasma trough concentration levels at steady state. CONCLUSIONS: Owing to the teratogenic potential and possible side-effects of oral retinoids, fertile women especially should be informed about the importance of strict alcohol abstinence during treatment and for at least 2 months after stopping therapy. In case of non-compliance with alcohol abstinence a post-therapy contraceptive period of 2-3 years should be recommended.     

Clinical, electrophysiological, and immunopathological study of peripheral nerves in Hansen's disease

Hansen's disease is a disease of peripheral nerves. Some patients develop peripheral neuropathy before the diagnosis of the disease, and others develop these complications after starting therapy. Electrophysiological (EP) studies were carried out in Hansen's disease patients. This work studied the neural deficits, electromyography (EMG) and motor nerve conduction (MNC) variables in different types of leprosy and the immunopathology of sural nerve tissue in patients with severe neural deficits. Forty leprosy patients had neurological examinations and EP study. Histopathological and immunopathological study of sural nerve biopsy specimens was performed for 10 patients with severe neural deficits. The results of the neurological study showed that there was involvement of cranial nerves, muscular system, motor reflexes and sensory system and trophic and vasomotor changes. EP study showed significant changes in EMG of abductor digiti minimi in patients as compared to controls. MNC variables of common peroneal nerve were abnormal in 80% of all patients, MNC of median nerve was abnormal in 72.5%, while MNC of ulnar nerve was abnormal in 70% and SNC of ulnar nerve was abnormal in 77.5% of the total. In conclusion, electrophysiological investigations have an important role in the detection of muscle denervation and neuropathic changes in leprosy patients. These investigations are safe, rapid and non-invasive techniques. On the other hand immunopathological study revealed that the degree of immune positivity correlated with the degree of nerve fibrosis.     

Effects of oral acitretin on contrast sensitivity and tear film function: a prospective study

The purpose of this prospective study was to investigate the ocular side effects of short-term therapy with oral acitretin (1 mg/kg/day) in 24 patients with severe and recalcitrant dermatoses. Apart from the routine ophthalmological examination, the following tests were performed: break-up time of tear film for the determination of its stability, Schirmer test for the assessment of lacrimal gland function, rose bengal staining for the detection of possible ocular surface damage and contrast sensitivity test for the evaluation of visual function. No statistically significant differences could be found between the pretreatment values of the assessed parameters and those obtained after 1 and 2 months of therapy. It seems reasonable, therefore, to suggest that ocular surface integrity and tear film and visual function are not affected by short-term oral acitretin administration.     

口服阿维A对106例儿童身高和骨骼发育影响的回顾性分析

【摘要】 目的 分析口服阿维A对患儿身高和骨骼发育的影响。方法 回顾性分析2007年3月至2021年1月于北京儿童医院皮肤科口服阿维A疗程 ≥ 1个月的106例患儿的临床资料和影像学资料。主要观察指标为身高和接近成年终身高，多因素logistic回归分析患儿身材矮小的影响因素，对已达接近成年终身高者采用非劣效性检验分析身高与遗传靶身高的接近程度。次要观察指标为骨龄、骨骺闭合情况，Wilcoxon符号秩检验分析患儿基线与末次随访时骨龄与时序年龄差值的差异和骨骺早闭情况。结果 106例患儿中，男62例，女44例，84例为脓疱型银屑病，10例为寻常型银屑病，11例为毛发红糠疹，1例为颜面播散性粟粒型狼疮，阿维A治疗剂量＜1 mg·kg-1·d-1，疗程1 ~ 90个月；0 ~ 18岁患儿96例，91例（94.8%）身材正常，5例（5.2%）身材矮小；83例阿维A单药治疗的患儿中，81例（97.6%）身材正常，2例（2.4%）身材矮小。二元logistic回归分析结果示，阿维A联合糖皮质激素治疗致身材矮小的风险比阿维A单药治疗增加76.57倍（OR = 77.57，95% CI 2.20 ~ 2 738.82，P = 0.017），而病种、性别、发病年龄和阿维A初始治疗年龄、疗程、平均日剂量对身材矮小的影响均无统计学意义（P值分别为0.988、0.214、0.087、0.078、0.066、0.350）。13例已达接近成年终身高者均身材正常，非劣效性检验示接近成年终身高均不劣于遗传靶身高（Satterthwaite = 0.23，P = 0.030）。比较45例患儿基线与末次随访时骨龄与时序年龄差值，两时间点差异无统计学意义（Z = -0.85，P = 0.250），且治疗前后均未出现骨骺早闭。结论 本研究初步显示口服阿维A治疗（剂量＜1 mg·kg-1·d-1，疗程＜90个月）对患儿身高和骨骼发育可能无明显影响。     

Keratoacanthoma centrifugum marginatum after photodynamic therapy with good response to oral retinoids and topical 5‐fluorouracil

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterized by progressive peripheral growth, and usually devoid of deep invasion. Different systemic (oral retinoids) or topical treatments have been reported, but there is not a well‐defined therapeutic protocol. We report the case of a KCM developing after photodynamic therapy (PDT) on the right leg of a 64‐year‐old woman. It was treated successfully with oral acitretin combined with topical 5‐Fluorouracil + salicylic acid for 5 months. This is the first case of KCM developing after PDT and successfully treated with oral retinoid combined with topical treatment.     

阿维A治疗四例基底细胞上皮瘤临床观察

我们采用口服阿维A及外用0.1％的维A酸霜成功治疗4例组织病理学证实为基底细胞癌患者。治疗结束时原位组织活检,原皮损部位组织细胞形态基本正常。治疗结束后每4周随访1次,观察肿瘤是否复发。4例患者随访6个月至4年不等,均未复发。在治疗及随访期间,实验室监测血常规、肝肾功能、血脂均正常。未见明显不良反应。我们认为口服阿维A可作为老年面部基底细胞癌患者的一种新的治疗方法。     

寻常型银屑病患者171例阿维A治疗相关不良反应及停药原因分析

目的:分析寻常型银屑病患者阿维A治疗相关药物不良反应（ADR）及停药原因。方法:收集广西医科大学第一附属医院2014—2019年使用阿维A治疗的寻常型银屑病患者292例,回顾性分析其中符合纳入与排除标准且能够定期随访的193例患者的临床资料,统计用药期间出现的ADR及停药原因。结果:193例中171例出现519例次AD...     

Cover Image,Volume 33, Issue 3

Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg⁻¹ day⁻¹, and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14‐60 years (mean 33 ± 14.7 years) and a course of 4‐48 months (mean 21.6 ± 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow‐up period of 6 months. Acitretin monotherapy is an effective, safe, and well‐tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.     

Long‐term results of acitretin therapy for hidradenitis suppurativa. Is acne inversa also a misnomer?

Background Hidradenitis suppurativa (HS) is a distressing chronic inflammatory skin disorder which affects predominantly the groins and axillae. In analogy to acne, oral isotretinoin has been considered in the treatment of HS, although there are strong indications that this drug has only a very limited therapeutic effect. During the past 25 years scattered case reports have described promising results of treatment with acitretin. Objectives To evaluate the long‐term efficacy of acitretin monotherapy. Methods A retrospective study in 12 patients with severe, recalcitrant HS who were treated with acitretin for 9–12 months at one Dermatology Centre in the Netherlands between 2005 and 2007 and were followed up to 4 years. The patients were men and infertile women. The efficacy of the treatment was rated by the patients on global maximum pain of nodules and abscesses on a visual analogue scale (VAS) as well as by physician global assessment. Results All 12 patients achieved remission and experienced a significant decrease in pain as assessed by VAS. In nine patients long‐lasting improvement was observed, with no recurrence of lesions after 6 months (n = 1), 1 year (n = 3), > 2 years (n = 2), > 3 years (n = 2) and > 4 years (n = 1). Conclusions Acitretin appears to be an effective treatment for refractory HS, leading to reduction of pain from painful nodules and reducing the extent of the disease for a prolonged period.     

DAPSONE INDUCED PERIPHERAL NEUROPATHY

Summary.— A further case of peripheral neuropathy has occurred in the course of dapsone therapy. It was predominantly motor in type, but a sensory element was present. It recovered completely after dapsone withdrawal. Electromyography and nerve conduction studies showed the neuropathy to be axonal in type.     

Dapsone-induced Peripheral Neuropathy

A young man with dermatitis herpetiformis developed fatigue and neurologic complaints 4 years after he began oral dapsone therapy. Neurologic examination and nerve conduction studies confirmed the presence of a combined motor and sensory peripheral neuropathy. The symptomatic improvement reported by the patient was supported by improvement in the nerve conduction studies after cessation of dapsone therapy. Substitution of sulfapyridine did not adversely affect the resolution of his neuropathy.     

Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy

Elephantiasis nostras verrucosa is characterized by chronic secondary, non-filarial lymphoedema due to recurrent lymphangitis, dermal fibrosis, and epidermal changes consisting of hyperkeratotic, verrucous and papillomatous lesions. Histologically, there is pseudoepitheliomatous hyperplasia. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes. In this study, rapid disappearance of the hyperkeratotic and verrucous lesions, remarkable flattening of the papillomatous nodules and improvement of lymphoedema occurred in three obese patients treated with etretinate in an initial dose of 0.6-0.75 mg/kg/day for 4-6 weeks. Monitoring of plasma concentrations of etretinate, acitretin and 13-cis-acitretin by HPLC revealed sufficient short-time absorption (4 h) and bioavailability of the drug (30 days; two out of three patients). Long-term maintenance therapy in one patient produced a remarkable improvement in the lymphoedema; another patient relapsed after discontinuation of the etretinate and responded again after this was reintroduced. In the third patient treatment was withdrawn because of an increase in triglycerides, but improvement persisted 6 months later. The clinical side-effects of oral retinoid therapy were moderate and well tolerated.     

神经导管修复周围神经损伤的临床应用

目的应用神经导管桥接缝合法,提高周围神经损伤修复疗效。方法应用可降解几丁糖-生物膜导管,使用套入桥接缝合法,代替以往的端端缝合法修复神经损伤,术后随访了解神经功能恢复情况。结果12例,其中8例感觉神经损伤,2例运动神经受损,2例长段神经移植。随访为6～20个月,8例感觉恢复S3或S3 ,1例运动恢复M3,1例M4。2例电击伤患者感觉功能恢复为S2。结论应用神经导管套入缝合法能有效修复周围神经损伤。     

A study on the management of hidradenitis suppurativa with retinoids and surgical excision

Background:

Hidradenitis suppurativa is a chronic skin condition involving the apocrine glandular zones. Affected patients may present with acute abscesses, but the condition often progresses to a chronic state with persistent pain, sepsis, sinus tract, fistula formation, purulent discharge, and dermal scarring. The treatment of patients with severe disease can be difficult and may require complex surgical intervention.

Materials and Methods:

For this study, we selected 30 patients from the outpatient department. The patients were divided into two groups of 15 patients each. In patients of group I, oral acitretin 0.5 mg/kg body weight was given alone. Oral acitretin was given for a period of 12 weeks, and follow-up of the patients was done every 4 weeks for a period of 6 months. In patients of group II, oral acitretin 0.5 mg/kg was given plus a wide surgical excision was done.

Results and Discussion:

In our study, the commonest site of involvement of hidradenitis suppurativa was axilla in 83.3% patients, perineum was involved in 13.3% patients, and periumbilical involvement was seen in 3.3% patients. The commonest clinical feature was nodules seen in 90% patients; pain was seen in 60% patients, dermal scarring in 73.3% patients, malodorous discharge in 33.3% patients, abscess in 30% patients, and fistulous tracts were seen in 20% patients. The recurrence rate was low (20%) in group II patients in whom oral acitretin was given plus surgical excision was done as compared with group I (40%) in whom oral acitretin was given alone.     

Acitretin for lichen amyloidosus

We present two cases of lichen amyloidosus treated with retinoids. A 57-year-old Vietnamese woman has had extensive generalized recalcitrant lichen amyloidosus for 23 years. Treatment with oral etretinate (25 mg/day) for 3 years, and later oral acitretin (10 mg/day) for the past 10 years, has controlled the pruritus and flattened the hyperkeratotic papules. Whenever the acitretin was ceased her symptoms flared within weeks. On each occasion reintroduction of acitretin was effective within 1-2 months. The second case is that of a 51-year-old Australian Aboriginal woman who had a 2-year history of lichen amyloidosus affecting her lower legs. A 2-month course of oral acitretin (25 mg b.d.) produced a marked improvement in both the pruritus and hyperkeratotic papules. She was then lost to follow up for 2 years, during which time her symptoms recurred.     

Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years' experience on 23 patients

BACKGROUND: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children. OBJECTIVES: The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago. METHODS: Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes. RESULTS: Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit +/- side-effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate. CONCLUSIONS: This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life-long treatment with retinoids.