Acne in Cystic Fibrosis: Tips for Prescribing Isotretinoin in the Genomodulatory Era

Antibiotic adherence is poor amongst people with cystic fibrosis (CF). Low-quality patient information leaflets (PILs), which accompany prescription antibiotics, with poor readability may contribute to poor antibiotic adherence, with the potential for antimicrobial resistance (AMR) development. The aim of this study was to examine the readability of antibiotic PILs used to treat CF lung infections. CF-related antibiotics (n = 23; seven classes: aminoglycosides, β-lactams, fluoroquinolones, macrolides/lincosamides, oxazolidinones, tetracyclines, trimethoprim/sulfamethoxazole) were investigated. Readability of PILs (n = 141; 23 antibiotics) from the EU (n = 40), USA (n = 42) and UK (n = 59) was calculated. Mean [± standard error of mean (SEM)] values for the Flesch Reading Ease (FRE) for EU, USA and UK were 50.0 ± 1.1, 56.2 ± 1.3 and 51.7 ± 1.1, respectively (FRE target ≥60). Mean (± SEM) values for the Flesch Kinkaid Grade Level (FKGL) for the EU, USA and UK were 9.0 ± 0.2, 7.5 ± 0.2 and 9.6 ± 0.2, respectively (FKGL target ≤8). US PILs were significantly shorter (P < 0.0001) in words (mean ± SEM = 1365 ± 52), than either UK or EU PILs, with fewer sentences (P < 0.0001), fewer words per sentence (P < 0.0001) and fewer syllables per word. The mean ( ± SEM) reading time of UK PILs (n = 59) was 12.7 ± 0.55 mins . Readability of antibiotic PILs is poor. Improving PIL readability may lead to improved health literacy, which may translate to increased antibiotic adherence and AMR avoidance. Authors preparing written materials for the lay/patient CF community are encouraged to employ readability calculators, so that final materials are within recommended readability reference parameters, to support the health (antibiotic) literacy of their readers.

We report here a case of a young female patient who developed sacroiliitis related to isotretinoin (13-cis-retinoic acid) use which completely resolved following discontinuation of the medication. Isotretinoin, a retinoid indicated for the treatment of severe cystic acne, has been associated with adverse effects, including musculoskeletal symptoms such as arthritis, arthralgia, myalgia and soft tissue calcification. Reactive sacroiliitis is a rare side effect. A small number of cases of sacroiliitis occurring in association with isotretinoin use have been described.1-3 A 20-year-old healthy woman was admitted to our department with complaints of myalgia, bilateral hip, pelvic and low back pain. She was not using any drugs except isotretinoin, which she had been using to treat acne for the previous 3 months (initial dose 30 mg/day for the first month, then increased to 40 mg/day for the following 2 months). Because of increased pain, the patient had stopped using the drug 15 days ago. On physical examination, sacroiliac joints were very painful and Gaenslen, Thigh Thrust, Patrick Faber and Mennel tests were strongly positive. Muscle power was normal (Medical Research Council scale 5/5). Laboratory examination showed that the erythrocyte sedimentation rate was 52 mm/h (normal range 0–20), C-reactive protein 2.75 mg/dL (0.0–0.5), creatine-kinase (CK) 43 U/L (30–200). Antinuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, C3, C4 were all negative. Blood chemistry, thyroid function tests and complete blood count were unremarkable. Screening for viruses and brucella was negative. Human leukocyte antigen (HLA)-B27 was positive. X-ray of pelvis and sacroiliac joint was normal. Magnetic resonance imaging (MRI) showed bilateral active inflammatory sacroiliitis with evidence of bone marrow edema adjacent to both sacroiliac joints. In dynamic contrast enhanced MRI, Fehn activity was measured 103% around the right sacroiliac joint and 75% around the left sacroiliac joint. These measures were compatible with prominent activity (Fig. 1). The patient was treated with prednisolone (15 mg daily slowly decreasing until suspension) and diclofenac sodium (75 mg daily) with gradual improvement over 2 months. After 6 weeks, the symptoms had completely resolved and the laboratory results had improved, so the treatment was stopped. There was no complaint and the laboratory results were normal on the sixth month of follow-up. The use of the Naranjo probability scale indicated a probable relationship between isotretinoin therapy and sacroiliitis.4 Isotretinoin is a retinoid that is used to treat cystic acne, comedonal acne and other diseases. Its most common side effects are mucocutaneous and ocular in nature (i.e., cheilitis, ocular sicca and decreased dark adaptation).5 Reactive sacroiliitis is a rare side effect. On physical examination and MRI findings, we see the symptoms related to sacroiliitis which are mentioned above in our patient. After isotretinoin treatment was stopped, the complaints in our patient vanished. Bilateral symmetrical sacroiliitis can be seen in seronegative spondyloarthropathies, although the presentation in this case is not characteristic of any of these disorders. The patient had no infectious conditions capable of initiating reactive arthritis and lacked both a history and symptoms of inflammatory bowel disease, psoriasis, uveitis, conjunctivitis or peripheral arthritis inconsistent with ankylosing spondylitis, enteropathic arthropathies or psoriatic arthropathy.6 The mechanisms underlying the induction of sacroiliitis by isotretinoin are not currently known. HLA-B27 was positive in our patient. It may be possible that patients with HLA-B27 could be more prone to developing sacroiliitis with isotretinoin use or sacroiliitis might have been triggered by isotretinoin.3 During isotretinoin treatment, patients may become colonized with Staphylococcus bacteria. Thus, it is reported in the literature that the frequency of incidence of perioral abscess formation, severe mucositis or angioedema, increase in patients having isotretinoin treatment.7 Cell-mediated autoimmunity which may develop with hypersensitivity reaction related to isotretinoin treatment may be responsible for multiple target involvement.5 We report here that isotretinoin treatment is usually used in acne treatment, may cause sacroiliitis development or trigger it in healthy people. We advise rheumatologists to be aware of this side effect. None.

AimThe trust has implemented the use of therapeutic drug monitoring (TDM) of teicoplanin on intensive care following research that identified great variability in population pharmacokinetics in children.1–3 The summary of...

Summary Isotretinoin (13-cis retinoic acid) is the most potent known inhibitor of sebum production. The multiple modes of action for isotretinoin, including suppression of sebaceous gland activity, normalization of the pattern of keratinization within the sebaceous gland follicle, inhibition of inflammation, reduction of growth of Propionibacterium acnes in a secondary manner and, as currently shown, normalization of the expression of matrix tissue metalloproteinases and their inhibitors make this compound the single most effective in the treatment of severe recalcitrant nodulocystic acne, and in the prevention of acne scarring. Several generic formulations for oral use have recently been introduced, in addition to the brand formulations Roaccutane and Accutane (Roche). This development, considering the high risk of teratogenicity associated with oral isotretinoin use, has led the European Commission and the European Medicines Agency (EMEA) to release a directive towards the harmonization of the Summary of Product Characteristics (SPC). This has similarities to US FDA regulations, a matter that caused the reaction of the Forum for the Improvement of Clinical Trials in Acne. Physician's experience, coupled with proper patient selection, dose adjustment or discontinuation of treatment, and routine monitoring for potential toxicity, has allowed the successful prevention and management of most adverse effects associated with isotretinoin.

The Clinical Pharmacology Sections in Drug Package Inserts: Do We Need to Reexamine the Basis?

Dear Editor: Henoch-Schonlein purpura (HSP) is a leucocytoclastic vasculitis that typically presents with a palpable purpuric rash. The disease primarily affects children and has rarely been seen in adults (3.4 to 14.3 cases per million)1. Hereby, we present a 20-year-old patient with HSP that developed during isotretinoin treatment for his acne. A 20-year-old man presented at our outpatient clinic with palpable purpuric lesions developed after the fourth week of isotreinoin (30 mg/day) treatment for severe inflammatory acne. Examination revealed multiple palpable purpura on the legs, 1 mm to 15 mm in diameter (Fig. 1). Furthermore, the patient had arthralgia in both ankles and knees. Complete blood count, liver and kidney function tests, coagulation test, routine biochemistry panel, and lung posterior/anterior graphy were normal. All of the following tests were negative: antinuclear antibodies, anti-neutrophil cytoplasmic antibody, cryoglobulins, hepatitis B surface antigen, anti-human immunodeficiency virus and anti-hepatitis C virus antibodies were. The patient's serum anti-streptolizin O, rheumatoid factor, immunoglobulin A (IgA), and complement levels (C3~C4) were normal. C-reactive protein level was 16 mg/L (reference range 0~6 mg/L). Erythrocyte sedimentation rate was 35 mm/h (Westergren method). He had no abdominal complaints like pain or rectal bleeding; fecal occult blood test was negative. Urinary sediment analysis was normal. During the taking of his medical history, the patient denied recent upper respiratory, gastrointestinal or genitourinary tract infections and he did not have any physical evidence of infection. The patient also denied any vaccination or drug use other than isotretinoin over the last 2 months. A skin biopsy of from one of the lower limb lesions showed leukocytoclastic vasculitis with IgA and C3 deposition (Fig. 2). On histopathological examination, in support of the relationship between vasculitis and the drug, quite a few eosinophilic infiltration in addition to perivascular neutrophilic infiltration was observed (Fig. 2B). According to these clinical and histopathological findings, the patient was diagnosed with having HSP. Isotretinoin treatment was discontinued; low-dose steroid therapy (fluocortolon 20 mg/day) was initiated and continued 3 weeks. All lesions disappeared by 2 weeks and the disease did not relapse during the 2 months' follow-up. Fig. 1 Palpable purpuric lesions on the lower limbs Fig. 2 (A) Dermal perivascular inflammatory infiltration (H&E ×40). (B) High power view of perivascular inflammatory infiltration including neutrophils with quite a few eosinophils and fibrinoid necrosis (H&E ×200). (C) Perivascular ... According to EULAR/PRES/PRINTO (European League Against Rheumatism / Paediatric Rheumatology European Society / Paediatric Rheumatology International Trials Organisation), the criterion of palpable purpura or of petechia with lower limb predominance is mandatory criterion for the diagnosis of HSP. Furthermore, at least one of the following criteria must be present: diffuse abdominal pain, IgA deposition in any biopsy, arthritis/arthralgia, and renal involvement2. The most common causes of HSP are infections of respiratory, gastrointestinal, and genitourinary tracts. Other well-known triggering factors of the disease are hepatic infections, inflammatory bowel disease, autoimmune rheumatic diseases, hematological and solid organ malignancies, vaccinations and adverse drug reactions to diverse drugs. Use of isotretinoin was the sole suspected cause of HSP in our case. Isotretinoin induced vasculitis is very rare in the literature. Dwyer et al.3 reviewed 11 isolated vasculitis cases, which could have been associated with isotretinoin and were gathered by manufacturer of isotretinoin. In the manufacturer's judgment, 5 of the 11 patients the leucocytoclastic vasculitis was associated with the use of systemic isotretinoin. There were no other factors other than retinoid use that may have caused vasculitis in these patients except for 1 patient who had streptococcal infection. Reynolds et al.4 reported a case of disseminated vasculitis, which developed 6 weeks after completion of isotretinoin treatment. However, some authors argued that this cause was controversial considering a serum half-life of isotretinoin5. Epstein et al.6 described 2 patients who developed severe vasculitis in whom one patient with Wegener's granulomatosis and the other patient with small-vessel angiitis, while receiving isotretinoin for severe cystic acne. Chochrad et al.7 reported a case of 'polyarteritis-like vasculitis' associated with isotretinoin. It is interesting that despite these early reports of vasculitis associated with isotretinoin, in a PubMed search we could not detect any other reports after 1997. The reason may be associated with a rare occurrence of cases, alternatively further cases may have not been reported. In addition, it is not possible to make a definitive diagnosis. Instead, the diagnosis of drug induced vasculitis is based on a temporal relationship between exposure to the agent and the development of vasculitis and the exclusion of other factors. In our case, we couldn't find any causal factor other than treatment with isotretinoin. Although rare, the clinicians should remember retinoid medications as a possible cause of vasculitis.

In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some “off-label” use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.

Opioid Metabolism

Background:Theoretical concerns about liver disease and vitamin A deficiency have limited the use of oral isotretinoin for troublesome acne in adolescents with cystic fibrosis.Methods:Oral isotretinoin was administered to nine patients...

Currently, the isotretinoin (13-cis-retinoic acid) package insert contains language advising the discontinuation of isotretinoin for 6 months before performing cosmetic procedures, including waxing, dermabrasion, chemical peels, laser procedures, or incisional and excisional cold-steel surgery. It is common practice to follow this standard because of concerns regarding reports of sporadic adverse events and increased risk of scarring. To develop expert consensus regarding the safety of skin procedures, including resurfacing, energy device treatments, and incisional and excisional procedures, in the setting of concurrent or recent isotretinoin use. The American Society for Dermatologic Surgery authorized a task force of content experts to review the evidence and provide guidance. First, data were extracted from the literature. This was followed by a clinical question review, a consensus Delphi process, and validation of the results by peer review. The task force concluded that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently or recently exposed to isotretinoin. Superficial and focal dermabrasion may also be safe when performed by a well-trained clinician.

Isotretinoin routinely causes mucocutaneous side-effects, such as cheilitis. Endocrine side-effects are not well documented, although reduced libido has been recognized recently. A 19-year-old male (weighing 60 kg and with a body mass index of 20.4 kg m−2) with no previous medical history developed unilateral left-sided gynaecomastia while taking oral isotretinoin for acne vulgaris (daily dose 20 mg for 1 month, 30 mg for 1 month, then 40 mg). He was taking no other medication or supplements, had never taken anabolic steroids and exercised daily. After 3 months of treatment, he noticed a firm, tender, left-sided subareolar mass, enlarging to 4.5-cm diameter, causing the areola to protrude approximately 5 mm above the level of the contralateral areola. Serum testosterone was 35.9 nmol L−1 (reference interval 8.7–29); a-fetoprotein and human chorionic gonadotropin were normal. Isotretinoin was discontinued, and the breast tissue returned to normal within 2 months, with no recurrence after 3 years of follow-up. Gynaecomastia in young adult males is uncommon, usually bilateral and is typically idiopathic in origin. Potential causes include hypogonadism and medications such as oestrogens, cimetidine, methyldopa, ketoconazole, spironolactone and tricyclic antidepressants. Obesity may lead to a similar appearance (pseudogynaecomastia). Isotretinoin has recently been linked to sexual dysfunction in both sexes, but a link is not proven: symptoms may have started after discontinuing isotretinoin and be long-lasting. Erectile dysfunction, loss of libido, anorgasmia and genital anaesthesia are reported; a minority of male patients have reduced testosterone. Gynaecomastia appears to be a very rare complication of isotretinoin use; only four previous cases have been reported in the literature. It is not listed as a potential side-effect in the Summary of Product Characteristics (SPC) leaflets for generic forms of isotretinoin, only being mentioned in the Roaccutane® SPC. The Medicines and Health products Regulatory Authority, in its updated online information leaflet (March 2022), lists gynaecomastia as a potential side-effect. The British National Formulary’s listing and the British Association of Dermatologists’ isotretinoin patient information leaflet do not mention gynaecomastia; however, reduced libido is stated. The European Medicines Agency and the National Health Service’s isotretinoin information webpage mention no endocrine side-effects. Cessation of isotretinoin was associated with resolution of the gynaecomastia; hence, we believe that it was responsible for it, although the mechanism of induction is unclear. An androgen–oestrogen imbalance has been suggested, leading to relative androgen deficiency. However, our patient had a high level of endogenous androgen, thought to be due to a high muscle mass, and entirely normal sexual function. Although uncommon, we would like to alert colleagues to the possibility of gynaecomastia resulting from isotretinoin treatment.

Background: Acne is highly prevalent among the young population in KSA. Oral isotretinoin is the most effective choice in the treatment of severe acne, which has potential adverse effects. Aim of the study: To assess knowledge and awareness of acne patients in Dawadmi Governorate about isotretinoin use and safety. Methods: This non-interventional cross-sectional survey was conducted through distribution of questionnaires over two months period (Sep. and Oct. 2019) in acne patients from the Dawadmi Governorate. Results: A total of 105 acne patients participated in the study, 77.1% were female and 22.9% were male, 88.6% knew about isotretinoin and its use and adverse effects. About (10.5%) of the participants used isotretinoin with mild acne which is contradictory to the recommended guidelines. Nearly 56.2% of the participants did not examine blood glucose before isotretinoin use, 9.5% of the participants did not examine blood glucose, lipid profile and liver enzymes before isotretinoin use. Not all of participants knew that depression (40%), inflammatory bowel disease (79%), osteoporosis (54.3%), and sunburns (22.9%) are isotretinoin associated risks. Most participants (89.5%) appropriately recognized teratogenicity as the greatest hazard concomitant with the use of isotretinoin. Despite that, 29.5% of the women did not know that they must stop administration of the drug at least 1 month before pregnancy. Half of participants (50.5%) did not know that they should not donate blood during use of isotretinoin and (61.9%) did not know they must stop administration of the drug at least 1 month before donation. Conclusion: This study shows that acne patients are not sufficiently aware of the convenient use of isotretinoin. Therefore, greater attention should be allocated on educating physicians and pharmacists to improve the safe use of isotretinoin. We recommend applying more effective regulations to restrict non-prescribed isotretinoin dispensing in KSA.

BackgroundIt is necessary to provide essential information to patients regarding medication to ensure safe and effective use. Patient Information Leaflets (PILs) are vital to fulfil this purpose. However, disparities in quality between multinational and local pharmaceutical companies PILs have been observed. The study aimed to assess and compare the completeness and quality of PILs available in community pharmacies from multinational and local pharmaceutical companies.MethodA cross-sectional comparative study design was used for evaluating 695 PILs (312 multinational, 383 local) across various therapeutic classes (antibiotics, anti-hypertensives, anti-diabetics, NSAIDs, and antidepressants). PILs were assessed against 31 criteria encompassing general information, dosage, indications, administration, interactions, safety information, pharmacokinetics, toxicology, storage, adverse effects, and pregnancy/breastfeeding details. Descriptive statistics, t-tests, chi-square tests, and odds ratios were included in statistical analysis.ResultSeveral criteria results showed excelling of Multinational PILs over local PILs. Significant differences favouring multinational PILs were observed in providing information on inactive ingredients (p = 0.024), adult-specific dosing (p = 0.0001), renal and hepatic dose adjustments (p = 0.018, p = 0.007 respectively), dosing in haemodialysis patients (p = 0.036), drug-drug interactions (p = 0.029), black box warnings (p = 0.027), clinical effects of toxicity (p = 0.045), and reporting adverse drug reactions (p = 0.04).ConclusionMultinational and local PILs, both performed well in providing basic information on active ingredients, brand names, contraindications, pregnancy, and lactation details. However, disparities among various aspects including inactive ingredient, specific dosing, dose adjusments and drug interactions between PILS of multinational and local pharmaceutical companies in Pakistan highlights the necessity for regulatory measures and industry initiatives to standardize PIL content. For ensuring patient safety and enhancing the quality of medication use it is essential to improve the comprehensiveness and clarity of PILs.

IntroductionAcne Vulgaris (Acne) is a common, chronic, cutaneous disorder associated with scarring, hyperpigmentation, and adverse psychological effects. The high prevalence of acne places a significant burden on healthcare systems worldwide due to the cost of treatment. The high usage of antibiotics in the treatment of this condition also has a significant impact on the prevalence of antimicrobial resistance. Isotretinoin is considered to be the most effective treatment for the management of severe acne; however, issues remain with inequitable access to this drug. General Practitioners (GPs) are ideally placed to identify and manage patients with moderate-to-severe acne; however, in many countries the prescription of isotretinoin is limited to secondary care. To the authors' knowledge, no review has been conducted to identify, map and analyse literature pertaining to GPs’ use of isotretinoin for the management of acne.MethodsAs recommended by the Joanna Briggs Institute (JBI), a three-step search strategy will be utilised for this scoping review. A search strategy will be developed using key words, search terms and controlled vocabulary suitable for each literature source. Both primary and grey literature will be eligible for inclusion in this review. Identified literature will be screened by two reviewers to identify relevant evidence. The full-text sources will then be evaluated by two independent researchers to extract relevant data. The findings of this review will be reported as a descriptive summary accompanied by a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.ResultsThis scoping review protocol outlines a systematic approach to map a broad range of sources and summarise existing evidence regarding GPs’ use of isotretinoin for the management of acne in primary care.ConclusionsThe objective of this scoping review is to comprehensively identify, map, and analyse literature pertaining to the management of acne using isotretinoin in general practice.Review registrationRegistered on Open Science Framework on 02/10/2025 (https://osf.io/rak3d/)

“Black box” warning: Wake-up call or overreaction?