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Spironolactone, Glycopyrronium tosylate for the treatment of paediatric primary axillary hyperhidrosis, New developments in dermatology, Psoriasis, Hidradenitis suppurativa, Biological agents in HS, Chronic hand eczema

Dr. Rémi Maghia

Dermatologist, Brest, France

Spironolactone: a genuine plea for the treatment of acne

Dr. William James, Dermatologist, United States

The management of moderate to severe acne is changing, due to a need to limit the use of oral antibiotics. Alternative tactics are increasingly being explored.

I saw a different speaker at this AAD Meeting present a strategy for treating acne without antibiotics. At a time when cyproterone acetate is no longer being used for acne vulgaris, public concerns about suicides related to isotretinoin are making this therapy appear suspicious, and combined oral contraceptives have become controversial, many articles are being published about the use of spironolactone for acne, including the publications by Brigitte Dreno's team. Let’s see how this American colleague presented and positioned this medication for us.

Spironolactone reduces testosterone production and acts by competitively inhibiting DHA and testosterone in the skin’s androgen receptors. It is an anti-androgen but has not been approved by the FDA.

It is underused despite recommendations to reduce the use of antibiotics (same high level of antibiotic use for acne between 2005 and 2013). Isotretinoin has remained at the same low level and the use of spironolactone has only slightly increased and is usually reserved for adult women.

There are reasons for this: non-approval by the FDA, an FDA black-box warning, a warning regarding cancer, the issue of potassium, and force of habit.

What about cancer? With studies with X 150 doses in animals, various cancers have been observed. Hence the black-box warning, which is now difficult to withdraw. Two large-scale retrospective studies (involving 2.3 million and 1.29 million women) did not find any association with breast, uterine or ovarian cancer.

Potassium monitoring: a study (JAMA Dermatol 2015) with 967 female patients concluded that K monitoring is not necessary in healthy young women. It is nonetheless important to verify whether the patient has heart or kidney disease or problems with high blood pressure. Certain medications should be verified, including: ACE inhibitors, NSAIDs, Trimethroprim-Sulfamethoxazole, and K and salt supplements.

The AAD guidelines are contradictory: on the one hand, the AAD allows the use of spironolactone in certain selected women, with no need to monitor K levels in plasma, and recognises that studies have proven that there is no association with breast cancer. But unfortunately in another chapter of the document, these guidelines say the opposite.

Efficacy for acne: the experiences of 600 female patients via three studies published in 2017 showed full clearance or marked improvement for the majority of the patients. The most common side effects are menstrual irregularities that can be managed with oral contraception, whose concomitant use improves the results and protects against pregnancy. Regarding pregnancy: theoretical risk of feminisation of a male foetus from six to 11 weeks. This was demonstrated in rats at 5 X the human dose and has never occurred in humans. Regarding breastfeeding: the American Medical Association and WHO consider the use of spirolactone to be compatible with breastfeeding.

The side effects are as follows: diuresis (29%), dizziness, menstrual irregularities (22%), breast tension; low blood pressure is uncommon (5% average decrease in blood pressure in healthy patients).

How should it be prescribed?

At what dose? From 50 to 200mg – the author starts at 100mg. Oral use with food to increase bioavailability. Evaluation after three months. Recommend contraception. If menstrual irregularities or breast tension, add oral conception; an implant is possible.

The author considers it a “superb” acne treatment for all women, not just acne-prone adult women, and an effective hormonal treatment. Here is his protocol:

When taking 100mg in the evening, few side effects – 85% of patients showed improvement and 40% full clearance. If no full clearance, can increase to 150mg if almost cleared or to 200mg if the response is moderate.

Around 81% of patients end up obtaining clearance. Combined oral contraception can be used in association with antibiotics.

For what indications?

Antibiotic failure

Response to antibiotics, but lack of maintenance with topical agents

No clearance with combined oral conception

Relapse after isotretinoin

As first-line treatment for acne-prone women? Yes for the author.

For all women? Yes, according to the author, adult women are not the only ones who respond, and not only those with acne on the lower face or acne affected by menstruation.

Keep in mind that in France, this is still an off-label use. Let's hope that Brigitte Dréno's hospital clinical research programme on spironolactone for this indication will provide support for this attractive therapeutic option.

Glycopyrronium tosylate for the treatment of paediatric primary axillary hyperhidrosis

Prof. Lawrence F. Eichenfield, Dermatologist, United States

This topic was addressed during the last plenary session of “What's New in Dermatology” (paediatric dermatology section), by Pr Eichenfield from San Diego.

He evoked the publication by Hebert et al, Pediatric Dermatology 2019. I thought he supplemented the information I gave you earlier on the issue of hyperhidrosis and psychiatric disorders.

This was a post-hoc analysis involving children aged nine to 16 years who had had primary axillary hyperhidrosis for more than six months, with an ASDD sweating severity score >4, sweat production >50mg/5min for each underarm, and an HDSS hyperhidrosis severity score >3.

They were treated via daily application of the product, an anticholinergic agent, with a towelette for four weeks. Responders were defined as having a four-level decrease in the ASDD score. At four weeks, 60% of the treated patients had reached the objective, vs 13% for the vehicle, which was particularly significant.

Side effects: mostly moderate and transient, seldom leading to cessation of treatment: mydriasis 16%, blurred vision 12%, dry mouth 24%. Some cases of oropharyngeal pain.

The product has been approved for ages nine and up in the USA: it is the first anticholinergic agent indicated as a topical treatment for adults and children aged nine and over.

The 2019 AAD Meeting is now over and I would like to take this opportunity to thank Bioderma/Naos for their remarkable support for this report and say how pleasant and constructive it was to work alongside Lise, Nicole and Géraldine.