The effect of isotretinoin on biotinidase activity.

BACKGROUND: Among the reaction and effects of isotretinoin, mucocutaneous reactions, xerosis and erythema of the skin as well as elevation of liver enzymes and lipids except high density lipoprotein have been reported. OBJECTIVE: Since biotinidase is mainly produced in the liver and partial biotinidase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activity were studied. METHODS: Forty-two (n = 42) patients with severe cystic acne had liver function tests, lipid estimations, serum biotin as well as biotinidase activity evaluations before (value 1) and on the 30th day (value 2) of treatment with isotretinoin monotherapy (Roaccutane 0.5 mg/kg/24 h). The same laboratory tests were evaluated in 50 controls only once. Moreover, the effect of isotretinoin on a known plasma biotinidase activity was evaluated after incubation in vitro with various concentrations of the drug. RESULTS: A statistically significant elevation of liver enzymes and lipids, except high density lipoprotein, was observed at the end of this study. On the contrary, biotinidase activity was found to be significantly decreased as compared to the initial values (value 1 = 4.70 +/- 0.89 nmol/min/l, value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001) and to controls (5.2 +/- 0.9 nmol/min/l vs. value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001). Additionally, biotin levels showed no significant alterations and the in vitro incubation of the enzyme with various concentrations of the drug exhibited no effect on its activity. CONCLUSION: It is suggested that isotretinoin isomers-metabolites act in the liver, resulting in low biotinidase activity.     

Lipoprotein (a) in patients with psoriasis: associations with lipid profiles and disease severity

Background  Lipoprotein (a) [Lp(a)] is a genetically determined molecule whose role has been implied in cardiovascular pathology, and whose levels have been reported to be elevated in patients with psoriasis.
Aim  To assess the serum levels of Lp(a) in patients with psoriasis, and to investigate the associations of Lp(a) with other lipids and with psoriasis severity.
Methods  Thirty-four patients with psoriasis and 26 healthy control subjects took part in the study. Serum levels of Lp(a) and total, high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) cholesterol fractions were measured in all participants. The levels of triglycerides and total cholesterol were measured using enzymatic colorimetric tests; HDL and LDL cholesterol concentrations were determined by precipitation methods; the VLDL concentration was calculated according to the formula: VLDL cholesterol = triglycerides/5.
Results  Patients with psoriasis showed significantly higher serum levels of Lp(a) relative to controls. Even when controlling for normolipidemic vs. hyperlipidemic status, abnormal levels of Lp(a) (> 30 mg/dL) were observed significantly more often in patients than in controls. In both patients and controls, Lp(a) levels correlated positively with total and HDL cholesterol levels. In patients, Lp(a) levels correlated positively with psoriasis severity.
Conclusions  Lp(a) may be a factor contributing to an increased cardiovascular risk in patients with psoriasis. A pathogenetic link may exist between this lipoprotein and psoriatic pathophysiology.     

The effect of silymarin on liver enzymes in patients taking isotretinoin: A randomized clinical trial

The aim of the present study was to investigate the effect of silymarin (Livergol) on liver enzymes in patients taking isotretinoin (Roaccutane). In this double‐blind clinical trial, 74 patients with acne and taking isotretinoin were randomly assigned into intervention (N = 37) and control (N = 37) groups. The intervention group received a 140 mg Livergol capsule per day for 30 days. The control group received a starch‐containing capsule as a placebo once a day for 30 days. Liver enzyme levels were measured before and after the intervention. The data were analyzed using chi‐square test, Independent t test, paired sample t test and analysis of covariance (ANCOVA). The results showed no statistically significant difference between the intervention and control groups at the beginning of study in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (p > .05). At the end of the study, a statistically significant difference was observed between the two groups in levels of AST and ALT (p < .05). Livergol prevented liver enzymes from increasing, so it can be used as an effective, low‐cost, and low‐complication treatment for the problem of increased levels of liver enzymes following the use of isotretinoin.     

Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: role of the enzyme paraoxonase-1

Background Psoriasis is a chronic, inflammatory skin disease associated with abnormal plasma lipid metabolism and with a high frequency of cardiovascular events. Modifications of plasma lipids and an increase in the levels of biochemical markers of lipid peroxidation have been reported in subjects with psoriasis, suggesting a relationship between psoriasis, lipoproteins and oxidative damage. Objectives To investigate further the relationship between lipoproteins and oxidative stress in psoriasis. Method The levels of plasma lipids, lipoprotein(a) [Lp(a)] and markers of lipid peroxidation were evaluated in subjects with psoriasis (n = 23) and in controls (n = 25). In the same subjects, the activity of paraoxonase‐1 (PON1), an antioxidant and an anti‐inflammatory enzyme associated with high‐density lipoproteins, was investigated. Results The results showed higher levels of Lp(a) in the serum of patients with psoriasis compared with controls (P < 0·001). Higher levels of lipid hydroperoxides (P < 0·001) and lower PON1 activity were observed in the serum of patients compared with healthy subjects, confirming that psoriasis is associated with oxidative stress. The imbalance between oxidative stress and antioxidant enzymes, and the increase of Lp(a) serum levels was related to the extent and severity of psoriasis. Finally, our results demonstrated that Lp(a) levels were positively correlated with markers of lipid peroxidation and negatively related to PON1 activity, suggesting that subjects with higher levels of Lp(a) are more exposed to oxidative damage. Conclusions Our results provide further evidence that oxidative stress and impairment of the antioxidant system in the plasma of patients may play a role in pathogenesis and progression of psoriasis and related complications.     

Serum lipoprotein (a) levels and Behçet's disease: is there an association?

Background Behçet's disease (BD) is a multisystemic inflammatory disorder found in individuals with a particular genetic background. Hemostatic studies in BD support an imbalance towards a prothrombotic state at different levels. Lipoprotein (a) (Lp(a)) has atherogenic and thrombogenic properties. It is mostly under genetic regulation. We investigated the possible relationship between Lp(a) and BD. Methods Forty patients diagnosed with BD and 40 healthy controls were enrolled. The clinical characteristics of the patients were recorded. Serum total cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoprotein A1, apolipoprotein B, and Lp(a) levels of the two groups were assessed and compared statistically. Results All patients (100%) had oral aphthous ulcers. Thirty (75%) had genital ulceration, 37 (92.5%) had either erythema nodosum or papulopustular lesions, and 10 (25%) had eye involvement. Twelve (30%) had a positive pathergy test. Four (10%) had vascular involvement. The Lp(a) level of the patient population was 19.6 ± 18.8 mg/dL. This level was higher than that of the controls, but not statistically significant. The Lp(a) levels of the four patients with vascular complications were within normal limits. Conclusions Lp(a) is of interest, as it is a genetically determined parameter that was found to be high in BD patients in our study group. The levels were independent of thrombotic complications, perhaps suggesting a different role for this lipoprotein in the etiopathogenesis of BD. Further studies with a larger number of patients are essential to discover the exact role of Lp(a) in BD.     

Short‐term isotretinoin treatment decreases insulin‐like growth factor‐1 and insulin‐like growth factor binding protein‐3 levels: does isotretinoin affect growth hormone physiology?

Summary Background Isotretinoin is an effective treatment for acne vulgaris. However, it has numerous side‐effects. It was previously reported that serum growth hormone (GH) levels decreased with isotretinoin treament. Objectives To analyse whether isotretinoin has any effects on insulin‐like growth factor‐1 (IGF‐1), insulin‐like growth factor binding protein‐3 (IGFBP3) and GH levels. Methods Forty‐seven patients aged 21·5 ± 5·1 years (mean ± SD) with acne vulgaris were included in this study. Isotretinoin therapy was initiated at a dose of 0·5–0·75 mg kg^?1 daily and then adjusted to 0·88 mg kg^?1 daily as maintenance dosage after 1 month. Screening for biochemical and hormonal parameters was performed just before initiation and after 3 months of isotretinoin treatment. Results IGF‐1 and IGFBP3 levels decreased significantly after treatment (P < 0·01), while GH levels did not change. Post‐treatment, significant increases were seen in aspartate aminotransferase, total cholesterol, low‐density lipoprotein cholesterol, triglycerides and low‐density lipoprotein cholesterol/high‐density lipoprotein cholesterol ratio (P < 0·0001) while high‐density lipoprotein cholesterol levels were significantly decreased (P < 0·0001). Conclusions Isotretinoin therapy may have an effect on GH physiology, and further studies are needed to understand this association.     

ISOTRETINOIN FOR ACNE VULGARIS

Background. The clinical efficacy of oral isotretinoin in the treatment of severe acne is now well established and so are the clinical and laboratory adverse effects of the drug. Isotretinoin was first introduced in Saudi Arabia late in 1987. In this 7-year retrospective study, efficacy and side effects of isotretinoin are reviewed in Saudi patients with acne vulgaris seen in a university skin clinic in Riyadh, Saudi Arabia. Materials and Methods. A total of 262 patients had been treated with isotretinoin. Their case records were studied with reference to demographic data, clinical findings, dosage of isotretinoin, response to the drug, and the prevalence and severity of clinical and laboratory adverse effects. Results. Only 156 case records (69.9% women) could be evaluated. Most patients received 0.60 to 0.75 mg of isotretinoin per kg per day for a period ranging from 16 to 35 weeks (mean ± SD: 21.2 ± 3.3 weeks); a total cumulative dose of 75 to 146 mg per kg (mean ± SD: 104 ± 10.6 mg per kg). Approximately 56% of the patients had therapy-resistant moderate acne and only 14% had nodulocystic acne. Of the patients, 90.4% had an excellent response and 3.8% were poor responders. Adverse effects occurred in 99% of the patients, but in no case did they lead to discontinuation of the drug. Except for minor differences in prevalence, the clinical side effects were similar to those reported in the literature. Elevation of plasma triglyceride levels was the most significant laboratory adverse effect. Conclusions. This is the first report on the experience with isotretinoin in the treatment of acne in the Middle East. Moderate doses of isotretinoin are well tolerated and produce excellent results in Saudi patients with acne.     

Plasma dermcidin levels in acne patients,and the effect of isotretinoin treatment on dermcidin levels

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. Dermcidin (DCD) is an antimicrobial peptide released from eccrine sweat glands and sebaceous glands. Studies investigating the role of DCD expression in acne development are scarce. The aim of this study was to determine the relationship between DCD expression and acne vulgaris and the effect of oral isotretinoin treatment on DCD levels. Two groups (one patient group and one control group) were included in the study. The patient group consisted of 30 patients with acne vulgaris who were given oral isotretinoin treatment for 6 months until the cumulative dose was attained. Plasma DCD levels were investigated before and 6 months after treatment. The control group comprised 30 volunteer individuals without acne vulgaris or any inflammatory dermatosis. Of the patients, 24 (80%) had Grade 3, 3 (10%) had Grade 1, and 3 (10%) had Grade 4 acne vulgaris, as determined according to the Pillsbury scoring method. The DCD levels in the control group were significantly higher than those in pretreatment patients (39.53 ± 20.2 vs. 28.60 ± 20.12, p = .004). Additionally, pretreatment DCD levels were significantly increased after 6 months of isotretinoin treatment in the patient group (28.60 ± 20.12 vs. 35.07 ± 24.02, p = .012). The mean pretreatment global acne grading system score of 20.86 ± 4.43 was decreased to 5.17 ± 1.91 in patients after treatment (p < .001). This study indicated that DCD plays an important role in the pathogenesis of acne. It demonstrates anti‐inflammatory properties in acne vulgaris. Moreover, it was shown that isotretinoin treatment may improve acne vulgaris by increasing DCD levels.     

Effects of metformin on autoimmune immunoglobins and interferon-γ in patients with early diagnosed pemphigus vulgaris: a prospective clinical trial

The management of pemphigus vulgaris (PV) is challenging. This study aimed to evaluate the immunomodulating effects of metformin on PV. The study was conducted in two phases: in the first phase, patients received routine first-line treatment (prednisolone plus azathioprine) for 2 months, then in the second phase, metformin was added to this regimen for another 2 months. After addition of metformin to the first-line medications, significant reductions were seen in serum IgG1 (reduced from 534.92 ± 134.83 mg/dL to 481.58 ± 130.46 mg/dL, P < 0.001), IgG4 (51.83 ± 27.26 mg/dL to 44.50 ± 26.05 mg/dL, P < 0.001) and interferon-γ (277.99 ± 108.71 pg/mL to 45.05 ± 17.080 pg/mL, P = 0.03) concentrations. The suppressant effect of metformin was greatest on IgG4 (coefficient of variation 1.28), the dominant subclass of IgG involved in PV. Metformin could have immunomodulating effects on PV with controlling effects on steroid complications.     

Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris

One of the primary events in the pathogenesis of acne vulgaris is abnormal follicular keratinization. Since oral isotretinoin therapy reduces follicular hyperkeratinization in acne, our study has been designed to determine whether epidermal lipid composition of the epithelium of sebaceous follicles is affected by isotretinoin treatment.Noninflamed early comedones obtained from ten patients with nodulocystic acne before and after the 6th week of isotretinoin therapy (mean daily dose 0.7 mg/kg b.wt.) were used as probes of the hyperkeratinizing follicular epithelium. Comedonal lipids were analyzed by high-performance thin-layer chromatography. Oral isotretinoin caused a decrease of the comedonal glyceride fraction by 36% (P<0.01), whereas free sterols and total ceramides increased by 34% (P<0.10) and 19%, respectively. The changes of comedonal lipids were associated with a significant elevation of the free sterols/cholesterol sulfate ratio of 86% from pretreatment levels (P<0.05). The isotretinoin-induced changes of the comedonal lipid composition in direction to a pattern of epidermal lipids of normal desquamating stratum corneum are discussed as a possible comedolytic mechanism of oral isotretinoin treatment.     

Conversion from calcineurin inhibitors to mTOR inhibitors stabilizes diabetic and hypertensive nephropathy after liver transplant

AIM: To investigate if conversion to the mammalian target of rapamycin inhibitors(mTORi) improves renal function in diabetic and/or hypertensive liver transplant patients immunosuppressed with tacrolimus or cyclosporine.METHODS: The study included 86 liver graft recipients immunosuppressed with mTORi treatment after orthotopic liver transplantation(OLT), including all liver recipients with worsening renal function before conversion to mTORi(n = 55 patients) and recipients with normal renal function who converted to m TORi for other reasons(n = 31 patients). We identified patients with diabetes mellitus(n = 28), arterial hypertension(n = 27), proteinuria(n = 27) and all three factors(n = 8)(some patients have hypertension and diabetes and no proteinuria). The primary endpoint was evolution in renal function defined as the development in plasma creatinine as a function of diabetes mellitus(DM), hypertension(HT) or proteinuria. We required elevated serum creatinine for at least two weeks to define renal dysfunction.RESULTS: Only patients that converted because of renal failure with plasma creatinine levels 1.5 mg/dL showed an improvement of renal function(2.14 to 1.77 mg/dL)(P = 0.02). Patients with DM showed no improvement of serum creatinine levels(1.31 mg/dL to 1.37 mg/dL) compared with non DM patients(1.31 mg/dL to 1.15 mg/dL)(P = 0.01), HT patients(1.48 mg/dL to 1.5 mg/dL) with non HT patients(1.21mg/d L to 1.08 mg/dL) and patients with proteinuria(1.44 mg/dL to 1.41 mg/dL) and no proteinuria(1.31 mg/dL to 1.11 mg/dL). CONCLUSION: In OLT recipients with diabetes or hypertensive nephropathy, conversion to m TORi does not improve renal function but stabilizes plasma levels of creatinine. Proteinuria is not a contraindication to conversion to m TORi; it also stabilizes renal function. Conversion to m TORi should only be avoided in patients with diabetes, hypertension and proteinuria.     

Raised galactose plus galactose-1-phosphate blood levels in patients under PUVA therapy

Background PUVA has become a preferred method of treatment for vitiligo and psoriasis. However, 8-methoxypsoralen (8-MOP) as well as a high galactose diet may cause liver and kidney function damage and enhance cataract formation. Patients and Methods Twenty one patients aged 32 ± 2.6 yrs with vitiligo (N= 11) or psoriasis (N= 10) underwent eye-examination, liver and kidney function tests and galactose + galactose 1-phosphate (gal + gal P) blood evaluation using Porton-Cambridge Ltd reagents, before and after the 12th PUVA treatment during a 35–40 day study. Results All these functional tests including eye-examination were normal before and after commencing therapy. However, the mean gal + gal P blood levels (1.29 ± 0.41 mg/dl) were statistically elevated (2.95 ± 0.42 mg/dl) at the end of the study. It is suggested that 8-MOP either impairs liver function or acts as an inhibitor of the enzymes responsible for galactose metabolism. We propose gal + gal P blood estimation in all patients before and, at intervals, after the initiation of PUVA therapy in order to prevent as early as possible an additional risk factor for liver or kidney dysfunction as well as cataract formation.     

The effects of isotretinoin therapy on the biliary system

The aim of the present study was to investigate the potential effects of isotretinoin on the biliary system in patients with acne vulgaris receiving isotretinoin therapy. This was a preliminary retrospective study involving 40 patients with severe acne vulgaris who attended the dermatology clinic and were administered different doses (20 or 30 mg/day) of isotretinoin. Serum levels of AST, ALT, ALP, GGT, total bilirubin, direct bilirubin, and indirect bilirubin at the beginning and at the first month of therapy were scanned, recorded, and statistically analyzed. Total and indirect bilirubin levels at the first month of treatment in 30 patients, receiving isotretinoin at a dose of 20 mg/day, were significantly lower compared to the baseline values (p = .02 and p = .03, respectively), whereas AST and GGT serum levels were significantly higher (p = .003 and p = .006 respectively). No significant reduction in total and indirect bilirubin levels was detectable at the first month of treatment in 10 patients receiving isotretinoin at a dose of 30 mg/day; however, AST, ALP, and GGT levels were significantly elevated in these patients (p = .023; p = .004; and p = .001, respectively). To our knowledge, there is no previous study investigating the effects of isotretinoin on the biliary system, and, therefore, the present study is a preliminary one. Our findings implicate that low dose (20 mg/day) isotretinoin therapy can potentially reduce total and indirect bilirubin levels. Long‐term, large‐scale, prospective studies with patients receiving different doses of isotretinoin may provide more reliable information regarding the bilirubin lowering effects of isotretinoin and optimum dosing for achieving this clinical effect.     

Response of rosacea to isotretinoin

We have treated seven patients with severe rosacea with 1 mg kg^?1 day^?1 isotretinoin for 12 weeks. There were large reductions in numbers of papules and pustules (P < 0.001) small decreases in measurements of erythema (P < 0.01) and median values for severity were lower during and after treatment. There was evidence of relapse by 8 weeks after stopping isotretinoin. Side-effects were well tolerated and increases in serum lipids and indices of liver function had reversed by 4 weeks after treatment. We conclude that isotretinoin is effective in rosacea.     

Very low dose isotretinoin is effective in controlling seborrhea

Background: Excessive seborrhea, coarse‐pored skin, minimal acne and oily scalp hair comprise a well‐known clinical entity. It causes considerable concern, has social impact, and affects the quality of life in some individuals. Some patients seek treatment for seborrhea. No effective topical sebosuppressive medication is available. Oral isotretinoin is the only remedy for men. In women, oral isotretinoin is the most effective remedy, followed by antiandrogens. Patients and methods: Eleven patients in three groups were treated for 6 months with very low dose isotretinoin. The influence on seborrhea was measured during oral treatment with 5 mg/d, 2.5 mg/d, or 2.5 mg 3× weekly. Results: Sebum production, measured with Sebutape®, was reduced by up to 64 %. Acne lesions regressed by as much as 84 %. Follicular filaments were reduced by 66 %. Microcomedones were reduced on average up to 86 %. Quantitative bacteriology showed a reduction of Propionibacterium acnes but no increase of Staphylococcus epidermidis. Biopsies revealed a 51 % reduction in sebaceous gland size. With Bentonite?, a reduction of lipids was demonstrated with 2.5 and 5 mg isotretinoin/d but not with 2.5 mg 3× weekly. There was a shift within the lipid fractions: triglycerides dominated, followed by squalenes and free fatty acids. Conclusions: Good results were achieved in all patients. The small number of patients did not permit a statistical analysis of the three isotretinoin doses studied, but there was a tendency toward better results with the two higher doses.     

Influence of oral isotretinoin on hepatic and cutaneous P-450-dependent isozyme activities

Oral administration of isotretinoin (13-cis-retinoic acid) (6 mg/kg per day), 0.05% hexachlorobenzene (HCB) or both drugs simultaneously for 10 days to female Wistar rats caused a statistically significant induction of aminopyrine-N-demethylase (ADM), 7-ethoxyresorufin-O-deethylase (7-ERO-D) and erythromycin-N-demethylase (EMDM) in the liver microsomes. Oral administration of isotretinoin alone or together with HCB induced a marked induction of 7-ERO-D and EMDM in the skin. Administration of isotretinoin alone for 60 days resulted in the induction of EMDM in the liver microsomes, and in combination with HCB caused a statistically significant induction of all hepatic isozymes. HCB alone caused a marked induction of only 7-ERO-D in the skin. These results clearly show that oral isotretinoin is capable of inducing hepatic and cutaneous microsomal P-450-dependent catalytic activities. It remains to be elucidated whether the induction of these enzymes is of importance for the therapeutic action of isotretinoin.     

Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne

Background: Isotretinoin is well known in the therapy of acne papulopustulosa and acne conglobata. No study has investigated the pathophysiological changes of the skin of acne patients, especially when low dose oral isotretinoin is given in combination with topical tretinoin. Patients and methods: 28 patients were treated for 6 months with oral isotretinoin. In the acne conglobata group (A – C) patients were treated with 10 mg (Group A) or 20 mg isotretinoin (Groups B, C) in combination with topical 0.05 % tretinoin cream. Group C was treated the first 2 weeks with 0.05 % betamethasone valerate cream instead of tretinoin cream. In the acne papulopustulosa group, the patients received 0.5 mg isotretinoin/kg bodyweight and 0.05 % tretinoin cream, either alone (Group E), or with oral methylprednisolone during induction (Group D). Results: Acne conglobata – A reduction of inflammatory lesion by 87 – 94 % and of non‐inflammatory lesions by 81 – 88 % was achieved (Groups A – C). A reduction of sebaceous gland size by 35 – 58 %, sebum production by 90 – 95 %, follicular keratinization by 55 – 70 % and Propionibacteria by 33 – 73 % was seen (Groups B and C better than Group A). In Group A the amount of lipids was only reduced by 6 %, in Group B by 35 % and in Group C by 40 %. Acne papulopustulosa – Sebum excretion rate and follicular keratinization were reduced in Group D by 89 % and 50 % respectively, with isotretinoin alone by 94 % and 53 %. The amount of lipids was reduced in Group D by 40 % and in Group E by 21 %. Conclusions: Because of the efficacy and cost‐benefit relationship of isotretinoin in the treatment of acne compared to other therapeutic approaches, further use low dose isotretinoin in the described settings seems to justified.     

The influence of isotretinoin upon fibrinolysis in patients with acne

A patient with haemophilia A and acne was recently reported to have experienced increased bleeding during therapy with isotretinoin.¹ The aim of the present study was to investigate the influence of isotretinoin upon fibrinolysis, and more specifically upon tissue plasminogen activator (tPA) and tissue plasminogen activator inhibitor (PAI) levels, in haemostatically normal individuals. Thirteen patients with severe acne received a 4-month course of isotretinoin at a dose of 1 mg/kg per day. In all cases, the acne responded to therapy, and the patients did not show any evidence of unexpected bleeding or bruising throughout the study. Although all investigations remained within the normal range, tPA measurements rose significantly (P < 0·001) after 3 months' therapy compared with pretreatment values. Retinoids have been shown to stimulate tPA production in vitro from human endothelial cells.² Our results confirm that this can be demonstrated in vivo. Prior to therapy with isotretinoin. when all patients had inflammatory acne, PAI measurements were elevated in 12 of 13 individuals. The mean measurement of PAI decreased from 98.38 ± 63.30ng/ml prior to treatment, to 24·63 ± 15.2 ng/ml (P<0·01) in the eight patients who returned for blood tests 6 weeks after completing therapy. The decline in PAI levels appears to reflect the resolving cutaneous inflammation following treatment with isotretinoin, rather than a direct effect of isotretinoin on the synthesis or release of PAI. This study provides further evidence that tPA production is stimulated by isotretinoin, and that this, together with falling PAI levels, may accelerate tibrinolysis. There was no clinical evidence that haemostasis was impaired in these haematologically normal individuals. However, the influence of retinoids upon fibrinolysis in haemostatically compromised patients may be clinically relevant, and at the present time we would caution against the use of retinoids in patients with impaired haemostasis.     

Changes in plasma cholesterol and triglyceride levels after treatment with oral isotretinoin. A prospective study

Twenty men with nodulocystic acne were treated with oral isotretinoin (13-cis-retinoic acid) for four months. Plasma lipids and lipoprotein determinations were obtained before and during treatment to quantitate the effects of oral isotretinoin on lipid metabolism. Maximum isotretinoin-induced elevations in plasma triglyceride and cholesterol levels were 67% and 16%, respectively. Additional maximal changes included very-low-density lipoprotein cholesterol increases of 56%, low-density lipoprotein cholesterol increases of 22%, and high-density lipoprotein decreases of 10% from pretreatment values. Chronic increases in plasma cholesterol levels, increases in low-density lipoprotein cholesterol levels, and decreases in high-density lipoprotein cholesterol levels may predispose subjects to premature atherosclerosis. Because of the potential for unmasking an occult lipid or lipoprotein disorder, the plasma lipid and lipoprotein profiles of subjects receiving isotretinoin should be carefully monitored.     

Effectiveness of conventional, low-dose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study

Background The efficacy of conventional isotretinoin treatment (0·5–1·0 mg kg^?1 daily for 16–32 weeks, reaching a cumulative dose of 120 mg kg^?1) for acne has been well established. To date, there are many reports regarding the efficacy of low‐dose and intermittent isotretinoin treatment in patients with acne. Data comparing these three therapeutic regimens simultaneously, however, are unavailable. Objectives To evaluate the clinical efficacy and tolerability of low‐dose and intermittent isotretinoin regimens and to compare them directly with conventional isotretinoin treatment. Methods In this study, 60 patients with moderate acne were enrolled and randomized to receive either isotretinoin at 0·5–0·7 mg kg^?1 daily (group A), isotretinoin at 0·25–0·4 mg kg^?1 daily (group B) or isotretinoin at 0·5–0·7 mg kg^?1 daily for 1 week out of every 4 weeks (group C). The total period of drug administration was 6 weeks in group C, and 24 weeks in groups A and B. Evaluations included global acne grading system (GAGS) scores, lesion counts (inflammatory and noninflammatory), patient satisfaction and side‐effects. A 1‐year follow‐up evaluation after the end of treatment was also performed. Results Differences in GAGS scores were statistically significant between groups A and C (P < 0·001) and groups B and C (P = 0·044). There was no significant difference between groups A and B. For the number of inflammatory lesions, there were statistically significant differences between groups B and C (P = 0·048) and groups C and A (P = 0·005). There was no significant difference between groups A and B. For the number of noninflammatory lesions, there were statistically significant differences between groups B and C (P = 0·046) and groups C and A (P = 0·006). There was no significant difference between groups A and B. These results suggest that the conventional and low‐dose regimens have similar efficacy. Intermittent treatment had less effect than either conventional or low‐dose treatments. Patient satisfaction was highest in group B (3·76), followed by group C (3·31), then A (3·06), with statistically significant differences between groups A and B (P = 0·003) and groups B and C (P = 0·019) but no significant difference between groups A and C. This result suggests that the low‐dose regimen is superior to other regimens (conventional or intermittent) in terms of patient satisfaction. Side‐effects were more frequent with conventional treatment compared with low‐dose and intermittent treatments. One year after the end of treatment, two of 16 patients relapsed in group A, three of 17 patients relapsed in group B, and nine of 16 patients relapsed in group C. Conclusions Our study suggests that, when considering tolerability, efficacy and patient satisfaction, low‐dose treatment is most suitable for patients with moderate acne.