Case Study: Why Is This Young Boy's Atopic Dermatitis So Resistant to Treatment?

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

Why has this boy's chronic atopic dermatitis (AD) recently worsened, after years of ongoing treatment?

That's what Giovanna Malara, MD, of Grande Ospedale Metropolitano in Reggio Calabria, Italy, and colleagues wanted to understand when a 9-year-old boy presented to their clinic with continuing severe pruritus despite treatment.

As the authors related in Clinical Case Reports, on initial questioning they learned that the patient had been spending a lot of time at an equestrian center – a point of information that turned out to be an important factor in the eventual diagnosis. He had been living with chronic AD since he was about 1 year old.

Physical examination revealed diffuse dryness of the skin; scabs on his face, trunk, arms, and legs; and a serious pruritic plaque on the lower left leg. These findings, along with a review of the patient's medical history, confirmed the diagnosis of AD. Blood tests showed that the serum level of total immunoglobulin E was within the normal range.

In reviewing the patient's medical history, clinicians learned that he had undergone skin prick tests with negative results for respiratory and food allergies; patch tests had also ruled out contact dermatitis. For years, he had been treated with both topical steroids (including hydrocortisone butyrate 0.1% and mometasone furoate 0.1%) and inhibitors of calcineurin (tacrolimus and pimecrolimus), none of which had had much of a benefit. His physicians had then tried deflazacort oral solution at a dosage of 1 mg/kg/day for 20 days in several cycles. Even so, his condition flared up frequently, the patient said.

When he presented at the clinic for his first assessment, he "had visible Dennie-Morgan lines, inflamed, erythematous papules, and crusty plaques scattered over 75% of his face and body, resulting in an Eczema Area and Severity Index score of 19," noted Malara and co-authors.

The reddish plaque on his left leg had not responded to topical treatment with either steroidal or antimicrobial creams. In light of the considerable time the patient said he spent at the horse riding center in contact with horses, the medical team decided to perform a culture test of a skin-scraped specimen. This revealed Enterococcus faecalis (E. faecalis).

After antibiotic susceptibility testing, the team prescribed the antibiotic they considered likely to be most effective, and "treatment subsequently led to a rapid improvement of the infected skin lesion," the case authors reported.

Discussion

In recounting this case of a 9-year-old boy with chronic AD unresponsive to treatment, Malara and co-authors noted that the pathophysiology of the condition is complex, and that while it results from dysfunction in the skin barrier and an unregulated immune response, AD is also influenced by genetic and environmental factors.

Patients with AD are more vulnerable to bacterial, fungal, and viral skin infections, and these can become invasive if left untreated. The increased tendency to develop skin infections that is characteristic of AD appears to be related to several contributing factors. In addition to skin barrier defects, AD is associated with a decrease in antimicrobial peptides (AMPs) – a group of molecules that help to protect against bacteria, fungi, and viruses – and increased skin pH, or Th2 cytokines (such as IL-4 and IL-13), the case authors explained. "The reduction might be due to the suppressive effect of Th2 cytokines (present in higher quantities in AD) and a relative decrease in IL-17 (an inducer of AMPs)."

The authors cited two studies that identified Staphylococcus and Enterococcus spp. species from the ground of an equestrian center. This confirmed the patient's high probability of coming into contact with these bacteria, given his ongoing exposure to soil contaminated with horse feces.

"The most common bacterial skin infections in AD are caused by Staphylococcus aureus (S aureus) followed by Streptococcus pyogenes whose virulence is due to staphylococcal enterotoxins (superantigens)," Malara and co-authors explained. Among AD patients colonized with S aureus, over 80% of samples isolated from AD patients are superantigen-producing, which contribute to cutaneous inflammation and corticosteroid resistance.

Compared with the general population, people with AD are also at greater risk of colonization by methicillin-resistant S. aureus (MRSA), Malara and co-authors noted, adding that "MRSA skin and soft-tissue infections lead to a loop of AD." Similarly, "AD patients are at a higher risk of eczema herpeticum caused by the herpes simplex virus and fungal infection, such as tinea or yeast."

Conclusion

Malara and co-authors concluded that among AD patients, skin barrier defects, a decrease in AMPs, increased skin pH, or Th2 cytokines all have the potential to increase the risk of skin infections, particularly S. aureus infections. This particular patient, however, developed a skin infection caused by E faecalis, which is generally present in the gut and bowel.

"The combination of environmental factors (such as frequent contact with animal excrement) and a well-documented higher susceptibility of AD patients to skin infections go some way to explaining this unusual skin condition," the authors concluded.

Read previous installments in this series:

Part 1: Atopic Dermatitis: Reasons for Optimism

Part 2: Atopic Dermatitis: The Latest on Diagnosis and Assessment

Part 3: The Many Ways to Measure the Severity of Atopic Dermatitis