ATOPIC DERMATITIS, SEVERE

By Gary M. White, MD

Atopic Dermatitis, Severe

The low back of a young man with severe atopic dermatitis (AD) who scratches incessantly. Many prurigo nodules are seen. His IgE is > 30,000.


Treatment

Excellent detailed guidelines of care can be found in the Journal of the American Academy of Dermatology Volume 71, Issue 2, Pages 327–349, August 2014.

Always remember that if the patient is on chronic steroids and then you start a steroid-sparing agent that works, taper the steroid gradually to prevent adrenal crisis.

Consider an Immunodeficiency Syndrome

In infants and children with particularly difficult to control AD, and especially when there is frequent secondary infection, one may want to consider an immunodeficiency syndrome.

Condition Suggestive Features
Severe combined immunodeficiency (SCID) Failure to thrive, chronic diarrhea and/or recurrent infections
Wiskott-Aldrich Syndrome Mucosal hemorrhage. Eczematous skin rash with petechiae and sanguinous crust, platelet disorders, e.g. thrombocytopenia
Hyperimmunoglobulin E Syndrome Very high levels of serum IgE (>2000 mg/dl), inflammatory facial papules, repeated fractures and retained primary teeth. Pulmonary infection results in abscess formation and pneumatocele development. Chronic mucocutaneous candidiasis.
DOCK8 Deficiency The second most common cause of hyper IgE Syndrome. Elevated IgE and severe skin infection with bacteria, herpes, warts and molluscum

Topical Steroid Withdrawal

Topical steroid withdrawal or Red Skin Syndrome has been recently described and may be considered when the eczema "flares" after abrupt cessation of topical steroid use.

Dupilumab

Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13--key drivers of type 2 helper T-cell (Th2)-mediated inflammation--was proven highly effective for atopic dermatitis. A 12-week DBPCT of dupilumab monotherapy found that 85% of patients on dupilumab, as compared with 35% of those on placebo, had a 50% reduction in the EASI score [N Engl J Med. 2014 Jul 10;371(2):130-9]. In combination with topical steroids, 100% of the subjects in the dupilumab group met the criterion for EASI-50, compared with 50% in the placebo group. Dupilumab is FDA-approved for adults with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies, or the therapies are not advisable. Dupilumab has been studied in children. One study of 38 children aged 6-11 years and 40 adolescents, aged 12-17 years found dupilumab to improve the eczema 60-70%. Patients received either 2 mg/kg or 4 mg/kg by subcutaneous injection weekly for 4 weeks [Dermatology News April 2017]. Adverse events were minimal.

Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD [JAAD 2018;78;62–69].

Vitamin D Supplementation

Short-term daily oral supplementation with 5000 IU of vitamin D3 was safe and significantly outperformed placebo for lessening the signs and symptoms of AD, according to the results of a randomized, double-blind trial of 65 patients with moderate to severe disease [Dermatology News April 2017 from a study performed in Mexico City as reported at the Society for Investigative Dermatology]. At the beginning of the study, 59% of patients had insufficient serum 25(OH)D (20-30 ng per mL), and 39% were deficient (< 20 ng per mL).

Probiotics

In a 12 week, DBPCT of children 4-17 years of age with AD, the addition of probiotics greatly improved the SCORAD index and reduced the amount of topical steroids needed [JAMA Derm 2018;154;37]. The probiotic was given daily and contained 10 to the 9th colony forming units of Bifidobacterium lactis, B longum, and Lactobacillus casea.

Referral to an Allergist

Refer to an allergist in general in the following situations:

Any child with moderate to severe atopic dermatitis may benefit from a visit to an allergist. Food allergies are especially common in infants. The most classic history is itching or rash within 30 minutes of ingestion of a certain food. Allergen avoidance (e.g., dust mite) continues to be recommended although in practice, such intervention has a varied benefit.

Food Allergies

How common is at food allergy in a child with AD? 15% in mild AD and 50% in moderate to severe AD [Pediatrics 2015;136;e1530]. The positive predictive value of IgE test however is poor. Peanut allergy is increasing all over the world.

Peanut Allergy Prevention

Patients with severe AD but who are not peanut-allergic should be exposed to peanuts early on to reduce the incidence of peanut allergy [NEJM 2015;372;803].

An expert panel sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, issued clinical guidelines:

"Addendum Guideline 1 focuses on infants deemed at high risk of developing peanut allergy because they already have severe eczema, egg allergy or both. The expert panel recommends that these infants have peanut-containing foods introduced into their diets as early as 4 to 6 months of age to reduce the risk of developing peanut allergy."

So in the infant with severe AD, get an IgE to peanut and if negative, okay to proceed. If positive (may be false positive), refer to allergy.

Patch Testing

One study from Sweden showed that about a quarter of children with AD had positive patch testing, the most common being nickel, amerchol, and potassium dichromate. The yield for positive results was much higher if the child had significant involvement of the hands and feet [Acta Derm Venereol 2014 Nov 04].

Systemic Steroids

Systemic steroids are very effective in treating flares but their side effects must be clearly and completely discussed with the patient. Prednisone 1mg/kg initially and tapered over 2-3 weeks or for adults intramuscular steroids (e.g., 40-60 mg. Kenalog) may be given.

Bleach Baths

For patients with treatment-resistant atopic dermatitis, bleach baths can be have been recommended. However, a recent study showed that a four-week, twice-weekly regime of diluted bleach baths was not more useful than water baths alone in reducing S. aureus colonization/infection and improving AD [J Dermatolog Treat. 2016;27:156-62].

Vitamin D

For patients with recurrent Staph infections, Vitamin D supplementation seems to decrease the prevalence of Staph.

UVB

Narrowband UVB is an effective treatment of AD, especially for maintenence. It should not be initiated when the patient is flaring as it may aggravate the disease. It may be used in children as young as 3 years of age if they can tolerate being in the booth. Usually for the very young, the parent totally covers up and accompanies the child into the booth. The parent accompanying the child may be necessary continuously or just for the first few sessions.

Cyclosporin

CSA is perhaps the favorite agent for control of severe disease and works in nearly every subset of AD. Unfortunately, it cannot be used long term because of renal toxicity. One study of European pediatric dermatologists showed that the majority chose cyclosporin (CSA) as their first-line agent for severe AD. Methotrexate (MTX) was their second choice. In a study comparing methotrexate (7.5 mg/week) with cyclosporin (2.5 mg/kg/day), both were equally effective [Eur J Pediatr 2012; 172:351–6]. CSA had a quicker onset of action, whereas MTX remission lasted longer upon cessation of the drug (average 9 months in one study). In another survey of pediatric dermatologist [JAAD 2017;76;281], first-line systemic agents used to treat severe AD in children were cyclosporin (45%), methotrexate (30%) and mycophenolate mofetil (13%).

Cyclosporin may be given 2.5-5 mg⁄kg per day. Benefit is seen within 2-3 weeks. The condition tends to relapse after stopping. In one study of children aged 7-14 yrs [Eur J Pediatr 2012; 172:351–6], cyclosporin 2.5 mg/kg/day (oral solution, 100 mg/ml, diluted in juice and administered in two divided doses) was used.

Methotrexate

Methotrexate is perhaps the preferred oral agent for long term therapy. In one study of 31 patients, methotrexate was found to be effective or very effective in 75% and ineffective in 25% [Int J Dermatol. 2014 Aug;53(8):1037-41]. In another study of children aged 7-14 years, the following protocol was used [Eur J Pediatr 2012; 172:351–6]:

For children on MTX who do not respond, the MTX PG3 assay has been used to see if the dose is sufficiently high SAN Aug 2013. For those who don't respond and levels are below 30 nmol/L, one expert suggests increasing the dose.

Azathioprine

Azathioprine is effective in both adults and children with AD and seems comparable in efficacy to methotrexate [J Allergy Clin Immunol 2011;128;353-9]. In a study of 82 children with AD treated with azathioprine [JAAD 2015;72;108], the mean age was 8.3 years, and the dose 2.4 mg/kg for normal thiopurine methyltransferase. Forty-one percent of patients had abnormal blood tests. Five patients stopped because of adverse effects: neutropenia, elevated LFT, headache, recurrent chest infection, and recurrent herpes labialis.

Another study [BJD 2015;172;1122], found that about half of adult patients who begin treatment with azathioprine for severe AD retain the clinical benefit of the treatment after 1 year and tolerate the treatment without significant adverse effects. The other half of patients discontinue within the first year either due to lack of benefit or to adverse effects, predominantly GI disturbances.

Apremilast

A pilot study of 16 patients using apremilast in the treatment of atopic dermatitis showed encouraging results [Arch Dermatol. 2012;148:890–897].

Tofacitinib

The Scoring of AD index decreased by 66.6% in 6 patients with AD treated with tofacitinib [JAAD 2015;73;395–399].

Mycophenolate

Mycophenolate mofetil (2 gms/day in adults) has also been used in severe cases [BJD1999;141;154].

Daily Wet Wraps with Potent Topical Corticosteroids

One can illustrate the application of wet wraps in the office. See atopic soak and smear.

Omalizumab

Studies are ongoing to see if anti IgE therapy is helpful for AD. Some studies have shown benefit for omalizumab in treating severe AD, even in patients with high IgE [Clinical and Exp Derm 2013;38;496-500] but other studies have not. In the UK, omalizumab is licensed for patients with serum IgE levels of < 700 IU/ml, but is not contraindicated in patients with higher levels. Some argue omalizumab may be beneficial in the subset of AD patients with lower IgE levels.

IgE-Specific Immunoadsorption

IgE IA was used in two patients with very high IgE levels (40,848 and 111,696) with benefit [JAMA Derm 2014;150;1350]. Patient 1 had a 48% reduction in SCORAD at week 17. Patient 2 had a 65% reduction at week 25.

Rituximab

Six patients have been reported to have improved significantly to rituximab 1000 mg IV two weeks apart with response within 4-8 weeks.

Ustekinumab

Ustekinumab does not seem to work for AD. A study of 33 patients with moderate-to-severe AD compared did not find a difference between ustekinumab and placebo [Exp Dermatol. 2016 Jun 15.]. See also BJD 2017; 177;419–427.

Itraconazole

A small subset of patients may respond to continuous oral itraconazole [JEADV 2016;30;873], e.g. 100 mg BID followed after clearing to 100 mg/day.

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