DermHelpCentral

Lab Testing When of Isotretinoin

Article: British Journal of Dermatology, August 2022

Is routine laboratory testing in healthy young patients taking isotretinoin necessary - a critically appraised topic
Andrew Affleck et. al.

Abstract
Adverse events were very rare (less than 1 in 10,000) and either idiosyncratic or not preventable by monitoring, were accompanied by symptoms, or occurred in identifiable predisposed individuals that may benefit from monitoring because of pre-existing conditions.

Recommendation for clinical care: We could not find evidence to support the benefit of monitoring to detect adverse events. We suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary and risks detecting non-serious biochemical abnormalities. However, we recognise that new information about adverse events may change that recommendation.

Br J Dermatol. 2022 Aug 20. PMID: 35986616

Spironolactone & Acne Review Article

Use of spironolactone to treat acne in adolescent females
Pediatric Dermatol. 2021 Jan;38(1):72-76.

Spironolactone is a safe, effective long-term alternative to systemic antibiotics for the treatment of acne in adolescent women. The article’s authors are pediatric dermatologists at the Mayo Clinic.

Download Spironolactome Acne Tollefson,

Hormonal Testing for Acne

Hormonal Evaluation of Acne

 

These hormone tests are best taken between 8:00 and 10:00 am during the first half of the menstrual cycle. They may include:

• Testosterone
• Sex hormone binding globulin (SHBG)
• Free androgen index (FAI)
• Dehydroepiandrosterone sulfate (DHEAS)
• 17-hydroxyprogesterone
• Synacthen test of adrenal stimulation by adrenocorticotrophic hormone (ACTH)
• Luteinising hormone (LH) and follicular stimulating hormone (FSH)
• Prolactin
• Cortisol
• Dexamethasone suppression test

From the AAD:

Hormonal testing and interpretation of testing is complex. A typical hormone-screening panel includes free and total testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, luteinizing hormone, and follicle-stimulating hormone.^49,51-54,165 Growth hormone, insulin-like growth factor, lipid levels, insulin, sex hormone–binding globulin, free 17-β-hydroxysteroids, free androgen index, prolactin, estrogen, and progesterone may also be abnormal in those with severe acne.^{52,54-56,165,169} Insulin resistance may also represent a risk factor for acne in certain patients.¹⁷⁰ Patients with abnormal test results, or in whom there is a persistent concern for a hormonal disorder, should be further evaluated by an endocrinologist.

 

Marius Rademaker's Talks on Isotretinoin and Atopic Dermatitis

Marius Rademaker practices dermatology in Hamilton, New Zealand.
He has been at the forefront of research into the use of isotretinoin for acne and other disorders as well as the treatment of atopic dermatitis with methotrexate.

Here are notes from his presentations at Hot Spots in Dermatology
August 17 - 19, 2018, Kahuku, Hawaii

1. Isotretinoin:  Download Notes from Marius Rademaker’s Talks on Isotretinoin
2. Methotrexate: for Atopic Dermatitis : Download Marius Rademaker on Atopic Dermatitis

Key References:

1. Download Isotretinoin- Dose Duration Relapse

2.We do not have a pdf.  Here is the citation + the abstract:

Methotrexate for treatment of atopic dermatitis in children and adolescents

Marius Rademaker et. al.

Int. J. Dermatoil 2014 https://doi.org/10.1111/ijd.12314 (06 March 2014)

Abstract: Low‐dose methotrexate is becoming established as a second‐line treatment for atopic eczema in the adult population, but there has been a paucity of data to support its use for this indication in the pediatric population.

Methods A retrospective review was undertaken of patients aged 18 years and under started on methotrexate between January 2005 and April 2010, at a hospital‐based dermatology department in New Zealand.

Results: Thirty‐one patients (17 females, mean age 10 years, range 3–18 years) were reviewed. Methotrexate was found to be effective or very effective in 75% and ineffective in 25%. The mean duration of treatment for those who responded to methotrexate was 14 months (range 2–38 months), 74% of patients were still on treatment at the time of last review. The most common adverse effect was minor nausea in four patients (14%) and non‐significant elevation of liver enzymes (four patients). No serious adverse effects were noted.

Conclusion: In our experience, methotrexate has a good safety/tolerability profile when used in low dose for the treatment of atopic dermatitis in children and adolescents and appears to be effective. Formal comparative studies are needed.

 

Low Dose Isotretinoin - Rademaker

Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us?

Rademaker M. Australas J Dermatol. 2013 Aug;54(3):157-62  Download Low Dose Isotretinoin Rademaker

Abstract: With 30 years of clinical use, it is appropriate to review the use of isotretinoin. We now understand that retinoids influence cellular growth, differentiation, morphogenesis and apoptosis, inhibit tumour promotion and malignant cell growth, exert immuno-modulatory actions and alter cellular cohesiveness. This has expanded the indications of isotretinoin from just acne and rosacea to a wide range of inflammatory and malignant skin disorders. While the standard dose of 0.5 to 1 mg/kg per day for 4 months to a cumulative dose of 120-140 mg/kg per day has served us well in the management of acne vulgaris, there is emerging evidence that much lower dosages (as low as 5 mg/day) are just as effective but have significantly fewer adverse effects. Relapse of acne vulgaris continues to be a problem but we are beginning to recognise that this is related less to the cumulative dose and more to the length of sebaceous gland suppression. Other factors important for relapse include a macrocomedonal pattern of acne, smoking and age, both younger (under 14 years) and older (over 25 years). After 30 years of use, we now understand why isotretinoin is such an effective drug. Not only does it clear acne in almost all patients, long-term remission can be achieved in 70-80% of patients with a single course. Important changes in the use of isotretinoin include using a lower daily dose for a longer period of time. New indications continue to emerge, particularly as a potential treatment for both intrinsic and extrinsic (photo) aging. Teratogenicity however, remains a very significant concern.

The Skin Microbiome Acne and Eczema

For decades researchers have argued that some of the skin’s microscopic residents are partly to blame for certain disorders, such as acne and eczema. Now, it seems, bacteria may be part of the treatment, too.  This NY Times article by Ferris Jabr is an introduction to this emerging field of research.

An article by Richard Gallo on Antimicrobials and Skin Disorders describes early research into this area.  Practical applications are still a ways off, but this may prove to be an effective approach for patients with acne and atopic dermatitis.

Abstract of Gallo article:
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

Pyoderma Faciale

Pyoderma faciale: Successful treatment with isotretinoin

Victor J. Marks, Robert A. Briggaman

J Am Acad Dermatol 17, 1062–106. 1987

Download Pyoderma faciale - pdf

Dr. Rademaker's Guide to Isotretinoin Dosing

Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris
Marius Rademaker, BM, FRCP, FRACP, DM   Int. J. Dermatol. 25. 518-23;2016

More complete notes.

Of 1453 patients treated with isotretinoin, 326 (22.4%) received a second course of treatment (study population). The remainder served as controls (n = 1127). Dosage varied from 10 mg/week to 1.1 mg/kg/d, cumulative dosage from 1 to >300 mg/kg, and duration of treatment from 8 weeks to 5 years. Compared with controls, patients who received a second course were more likely to be women (61 vs. 47%; P < 0.001) and received higher daily (0.71 vs. 0.58 mg/kg/d; P <0.001) and cumulative (126 vs. 101 mg/kg; P < 0.001) doses. Patients treated with very low doses (e.g. 10 mg three times per week) and/or low cumulative doses (e.g. 25–50 mg/kg) did not appear to relapse more often than controls. In Conclusion, neither daily nor cumulative dosages influenced relapse of acne patients treated with varying doses of isotretinoin as long as treatment was continued for ≥2 months after the acne had completely resolved.

Full article:  Download Rademaker Isotretinoin

Spironolactone and Acne

Spironolactone is a useful adjunctive therapy for acne in young women.  It is quite safe and can be very effective.  The following article is quite extensive, but may interest some readers.

Oral Spironolactone in Post-teenage Female Patients with Acne Vulgaris
Practical Considerations for the Clinician Based on Current Data and
J Clin Aesthet Dermatol. 2012 Mar; 5(3): 37–50.
Grace K. Kim, DO and James Q. Del Rosso, DO

Abstract: Oral spironolactone has been used for over two decades in the dermatological setting. Although it is not generally considered a primary option in the management of female patients with acne vulgaris, the increase in office visits by post-teenage women with acne vulgaris has recently placed a spotlight on the use of this agent in this subgroup of patients. This article reviews the literature focusing on the use of oral spironolactone in this subset of women with acne vulgaris, including discussions of the recommended starting dose, expected response time, adjustments in therapy, potential adverse effects, and patient monitoring.
Note: The Free Full-Text Open Access article is “everything you ever wanted to know about spironolactone but were afraid to ask.”     

Here is a brief, but informative, web-based resource on spironolactone and acne.        

Isotretinoin Option Grid

Isotretinoin (aka Accutane) is commonly used for severe acne because it is universally effective whereas other therapeutic options are less predictably successful.  However, many patients (or their parents) are frightened by anecdotal reports of bad side-effects they find about on the Internet.

The decision to take isotretinoin is value-based for patients or their guardians.  This tool may help to make the choice easier.

See: Isotretinon Option Grid.