Medical news on eczema by Dr Daniel Wallach – April 2020
Discover the second scientific publication in 2020 by Dr Wallach
“Preventing atopy: disappointment”,
“The most relevant diagnostic criteria for atopic dermatitis in China”,
“A European study on treatments for severe atopic dermatitis”,
“A new treatment: topical JAK-inhibitors”,
"The pain associated with atopic dermatitis",
Preventing atopy: disappointment
Skjerven HO, Rehbinder EM, Vettukattil R, et al. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.
Chalmers JR, Haines RH, Bradshaw LE, et al; BEEP study team. Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.
Before reading any articles such as those analyzed in our Medical News, be sure to verify the journal where it was published. Both these articles were taken from The Lancet, one of the most prestigious medical journals. This indicates that they are quality, reliable works likely to be highly influential. Unfortunately, their message is very disappointing: both appear to shatter all hopes today of preventing atopic dermatitis.
The Barrier Enhancement for Eczema Prevention (BEEP) study aimed to assess the benefits of applying an emollient daily to newborns at high risk for atopy. It was conducted across 15 British centers and included 1,394 newborns divided into a treatment group and a control group. Treatment lasted one year, and efficacy was evaluated based on the prevalence of atopic dermatitis at 2 years of age. Treatment compliance was deemed satisfactory. The results, however, were negative: 23% of children treated and 25% of children in the control group presented with AD. Furthermore, skin infections were more prevalent in the treated group. In conclusion, we are unable to recommend a preventive emollient treatment for at-risk newborns and infants.
The PRADALL study conducted in Sweden and Norway is a bit different. On the one hand, it involved healthy newborns from the general population, with and without a history of atopy. On the other hand, it compared four groups:
one with hydrating baths and face cream,
one with an early introduction of potential food allergens as a preventive measure,
one with both interventions (skin and digestive),
and one control group.
Treatment compliance was rather mediocre, with just one-third of parents deemed to have been compliant, which is not unusual for this type of preventive trial. Once again, the results were disappointing: at the age of 12 months, 8% of children in the control group presented with atopic dermatitis, compared to 11% in the emollient treatment group, 9% in the food allergen group, and 5% in the group with both interventions. The logical conclusion is that neither of these interventions is proven effective.
A European study on treatments for severe atopic dermatitis
Vermeulen FM, Gerbens LAA, Schmitt J, et al; international TREAT Registry Taskforce.
The European Treatment of atopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate-to-severe atopic eczema.
Br J Dermatol 2020, published online 18 February.
The TREAT register compiles all important data on the reality of treating patients with atopy. While we wait for developments with the imminent availability of Biologics and innovative small molecules, it is important to understand the current practices. Following similar investigations in the U.S. and the U.K., the TREAT working group has published the results of a study involving 229 dermatologists from 30 European countries. Most of the dermatologists are experienced and working in university hospitals (with only 18% independent). They therefore treat serious cases of atopy for which the usual topical treatments have been ineffective. They were questioned about their prescriptions of phototherapies and conventional systemic treatments. The purpose of the investigation was to compare “real-life” practices with the official recommendations, and to inform any future recommendations. This is even more important than you may think, given that the new treatments cannot fully replace the current ones due to issues of cost, tolerance, efficacy and availability.
With regard to phototherapy, prescribed by 85% of the dermatologists, narrowband UVB is the top choice, followed by PUVA. 95% of the dermatologists prescribed a systemic treatment. Ciclosporine is the most frequently prescribed first-line treatment (54%), then corticosteroids (32%) and methotrexate (30%). Azathioprine and mycophenolic acid are prescribed less often. Corticosteroids are most often used prior to an acute flare-up and/or when beginning treatment with an immunosuppressant. In terms of prescription factors, personal experience was the most widely cited. For many of these treatments, more information is needed on their long-term tolerance and efficacy.
A new treatment: topical JAK-inhibitors
Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T.
Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study.
J Am Acad Dermatol 2020;82:823-831.
An imbalance and hyperactivation of several cytokines are major contributing factors for atopic inflammation. The myriad of cytokines act inside the cells via a molecular system known as the JAK/STAT pathway. Inhibiting this system thus has anti-inflammatory effect. Several JAK-inhibitors are currently being developed as a very promising medicinal category in the treatment of atopic dermatitis as well as other inflammatory diseases such as rheumatoid arthritis. JAK-inhibitors are very different from Biologic drugs: they are small active molecules administered orally; topical formulations have also been developed; JAK-inhibitors act on several cytokines and have few side effects.
Pharmaceutical research on JAK-inhibitors is thriving. Oral treatments include upadacitinib, abrocitinib, baricitinib, gusacitinib, and tofacitinib. Topical treatments are of particular interest for atopic dermatitis and include tofacitinib, ruxolitinib and delgocitinib. The positive results for oral and topical JAK-inhibitors have been presented in several publications. For the purposes of this article, I will only highlight the most recent. First, there is the phase-3 trial for delgocitinib, which inhibits several kinases in the JAK system, developed in Japan in the form of an ointment with a concentration of 0.5%. The trial involved adults with a history of moderate to severe atopic dermatitis, according to the usual criteria. An initial double-blind four-week phase offered a comparison with an excipient, and a second open phase was conducted over 6 months. The results were analyzed according to the conventional AD parameters and are very positive: after four weeks, the average EASI score dropped by 44% in the delgocitinib group, versus 1.7% in the emollient group. After one month, 26.4% of treated patients obtained an EASI score of -75 (compared to 5.8% for the emollient group), which is quite a significant improvement. This rate increases to 35.8% after extending the treatment to six months (albeit with the possible addition of topical corticosteroids). The improvement in pruritus is significant and was achieved quickly, making it a point of interest. Local tolerance is good, with virtually no systemic absorption. These results will need to be corroborated by additional studies, but it is already apparent that JAK-inhibitors will soon offer an effective treatment to atopic dermatitis.
The pain associated with atopic dermatitis
Thyssen JP, Halling-Sønderby AS, Wu JJ, Egeberg A.
Pain severity and use of analgesic medication in adults with atopic dermatitis: a cross-sectional study.
Br J Dermatol 2020, published online 25 September 2019.
While pruritus has always been considered to be a key symptom of AD, pain has only recently been entered into the equation. In fact, it was revealed that a significant percentage of patients with atopy experienced pain. They describe this pain in various ways: tightness or burning sensations, pain when applying certain topical products, pain associated with cracks, especially on the hands and feet. The links between pruritus and pain are complex and likely unclear.
Danish population registers were used to correlate various pathologies with the consumption of medications. This study examined painful sensations in 3,834 adult patients with atopy (average age of 48), compared to 3,208 healthy subjects selected at random from the general population. The presence of pain was questioned during direct telephone interviews. No skin pain was reported in the general population. In the atopic population, skin pain was rated at an average of 4, on a scale from 0 to 10, for moderate AD (34% of the sample group) and 7 for severe AD (3.7% of the sample group, or 143 patients).
Pain is mostly associated with AD on the hands and feet, probably due to cracking in the skin, as well as on the chest for reasons unknown. Contrary to past studies, the face is not reported here as a particularly painful area when affected.
The authors were also able to analyze the atopic patients’ consumption of pain medication, which appears to be the same as the general population with regard to both common analgesics and opioids. It cannot be ruled out, however, that some patients with severe atopy, although rare, may use such medications. In light of the normal rate of consumption of pain medications, which is reassuring, the authors concluded that the usual treatments for AD, which are effective against pruritus, pain and discomfort, provide sufficient pain relief. This would also indicate that, unlike with other types of pain, the pain associated with AD correlates with pruritus and is sensitive to the treatment of eczema and pruritus.
Chronic hand eczema and therapeutic education
Tauber M, Lourari S, Bérard E, et al, SFD Education Therapy Group.
Positive change in hand care habits using therapeutic patient education in chronic hand eczema.
Contact Dermatitis. 2020;82:10-17.
The benefits of therapeutic patient education (TPE) for atopic dermatitis are well known. This study, based in Toulouse, indicates that TPE, provided under various models, may also be helpful in cases of chronic hand eczema (CHE). CHE is mainly a work-related disease, which includes several sub-categories based on the severity of the atopic, irritant and allergic factors. In all cases, treatment includes a potent topical corticosteroid, emollients, and a particular level of care with regard to cleansing, hand care products, and avoiding contact with substances that trigger the condition. 71 patients with CHE, including 14 healthcare professionals, participated in an individual TPE session lasting 60 to 90 minutes. During the session, good and bad practices were analyzed, and patients were given information on the aggravating factors and how to avoid them. In short, they were advised on how to properly wash and rinse their hands, using a suitable product (no dish soap!) and on using a quality emollient and a potent topical corticosteroid in sufficient amounts. They were also taught the scratching behaviors to be adopted and corrected if needed. All advice was provided in accordance with the French Health Authority recommendations.
Three months following this education session, significant improvement was reported in all the parameters analyzed. Negative behaviors, or behaviors which trigger the disease, were reduced significantly, as was the clinical severity and impact on quality of life. Professional productivity also improved. These conclusions are encouraging, even if a lack of control group limits their value. As a final note, this study was conducted in 2019 prior to the COVID-19 epidemic which has since imposed new hand-washing habits.
The cosmetic patch-tests conundrum
Horton E, Wilkinson M, Aalto-Korte K, et al.
A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.
Contact Dermatitis 2020;82:195-200.
Contact allergology is a complex science which has benefited greatly from the standardization of allergen test batteries. European experts formed a supervisory, or oversight, group and have already established a standard battery as well as specific batteries for allergens related to hair styling, photoallergens and sun care products. They are currently studying allergens found in other cosmetics. The first step was to gather information on the practices of the specialized centers. The investigation was thus carried out in 26 centers across 13 countries to confirm whether or not they tested sixty or so potential allergens found in cosmetics. These allergens are divided into several categories: 23 preservatives, 5 anti-microbials, 5 anti-oxidants, 6 emollients, 13 surfactants, a solvent (propylene glycol), and certain allergens specific to products designed for the underarms, lips, eyelids and nails. Not included on this long list are fragrances, which are part of a whole other series. The primary conclusion taken from this international investigation is the observation, or confirmation, that a considerably diverse range of practices are employed from one center to another. Will there ever be a consensus? That is the goal of the working groups who will compile the patch-test results in an effort to create a list of the most common cosmetic allergens. Hygiene habits and products vary so much from country to country; we can only wish them luck. In the meantime, the majority of experts test their patients in part using the standard battery and in part using their own products. However, the low concentration of allergens in most cosmetics leads to many false negatives. Finally, a standard cosmetic battery would also be helpful for testing intolerances to topical medications.
The role of contact allergy in eye complications on dupilumab
Raffi J, Suresh R, Fishman H, Botto N, Murase JE.
Investigating the role of allergic contact dermatitis in residual ocular surface disease on dupilumab (ROSDD).
Int J Womens Dermatol 2019;5:308-313.
Pistone G, Tilotta G, Gurreri R, Castelli E, Curiale S, Bongiorno MR.
Ocular surface disease during dupilumab treatment in patients with atopic dermatitis, is it possible to prevent it?
J Eur Acad Dermatol Venereol 2020, published online 27 January.
The authors of the first article observed in a retrospective series that atopy patients treated with dupilumab and presenting with an eye complication all had a previous ophthalmologic episode. These complications arising in patients on dupilumab vary: stubborn eczema on the eyelids, blepharitis, conjunctivitis, xeropthalmia, and at worst keratitis. The physiopathology of these conditions remains a mystery. Many hypotheses have been put forward, most of which are theoretical.
One hypothesis involves a contact allergy, triggered by an ingredient in the many topical skin and eye products applied by these patients. Nine patients were examined using patch-tests comprised of the standard battery and of ingredients in topical products and cosmetics. All of the subjects had a number of positive results, the most common being to surfactants and fragrances. The number of positive tests ranged from 3 to 15. All nine patients improved after avoiding the allergens responsible.
It seems logical to take this factor into account. In addition to atopy itself, which is of course always present, and the still poorly understood immunological and epithelial effects of dupilumab, a persistent contact allergy appears to be a relevant factor to be taken into consideration. In a short letter to the JEADV, G Pistone and the other authors all make the case, here as well as in a short series, that using artificial tears at the start of dupilumab treatment helps to prevent eye complications. Perhaps avoiding contact with triggering substances is applicable in this case as well.
"Dans la peau de Xavier", the first book for children written by Xavier Léost, expert patient
Interview with Xavier Léost, expert patient, about his very first book for children "Dans la peau de Xavier" (In Xavier's skin) dealing with bullying at school. A book inspired by his own personal story.
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