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News

Article

TNF Blockade Shows Effectiveness for Pediatric Cutaneous Crohn Disease; Interleukin-12/23 Inhibitors Also Promising

A recent case series reviewed the treatment patterns and effects of therapies on 89 pediatric patients with CCD.

In a review of 89 pediatric cases of cutaneous Crohn disease (CCD), researchers found that TNF blockade is an effective treatment option. Furthermore, they reported that interleukins (IL) 12 and 23 may be similar in efficacy. The review was deemed the largest of its kind to date.

Young girl interacting with artificial/graphic of intestines
Image Credit: © sdecoret - stock.adobe.com

Background and Methods

The review, published in Pediatric Dermatology,1 explored CCD, which is considered the least common dermatologic manifestation of Crohn disease. More common skin manifestations of the disease may include blistering, erythema nodosum, and skin tags, among others.2

CCD is characterized by granulomatous inflammation on the skin that occurs independently of gastrointestinal involvement or in the absence of intestinal disease altogether.3 These lesions typically manifest as small spots or plaques affecting areas like the arms, legs, or trunk.

Researchers McKay et al conducted a review of pediatric CCD cases. Utilizing a comprehensive search of PubMed, researchers identified 78 previously-reported cases from 1970 through June 2022. Only cases confirmed by skin or intestinal biopsy, and showing typical skin symptoms verified by dermatologists, were included. Eleven newly-reported, additional cases from a University of Wisconsin retrospective registry were also added.

Researchers collected relevant data, including patient demographics, disease status, symptoms, biopsy results, and treatments, with outcomes classified as "clearance," "partial clearance," "no effect," or "worsening."

Findings

The cohort consisted of 55% boys and 45% girls, with an average diagnosis age of 10.7 years. The most common site of CCD involvement was the genitals, affecting 75% of the cases, with vulvar involvement in 85% of girls and penile or scrotal involvement in 67% of boys. Boys were more likely to present with facial involvement compared to girls (33% vs. 10%).

Histological analysis revealed noncaseating granulomas in 84% of the cases.

For systemic treatment, corticosteroids were the most frequently used (60%), followed by antibiotics such as metronidazole (33%) and immunomodulators such as azathioprine (18%). Biologic agents, particularly TNF-alpha inhibitors, were used in 21% of cases, showing high efficacy with 94% achieving partial or total clearance of CCD.

Treatment outcomes varied, with 39% achieving total clearance and 48% partial clearance. However, a small percentage (9%) showed no effect, and 4% experienced worsening symptoms. Dual biologic therapy demonstrated promise in complex cases, exemplified by 2 cases where combination therapy led to remission of both intestinal and cutaneous symptoms.

Conclusions

Limitations of the review, as reflected upon by its authors, included a limited sample size and overall low heterogeneity.

"We propose that TNF blockade is an effective treatment for pediatric CCD," according to McKay et al. "We also propose that IL-12/23 inhibitors may be similarly effective and that the two biologics may work synergistically for improved cutaneous response as has been seen in refractory pediatric and adult [gastrointestinal] disease. Consideration of dual biologic therapy may be useful in pediatric patients requiring discordant therapies for their intestinal and cutaneous [Crohn disease]."

Moving forward, researchers noted that CCD can be confused with conditions such as hidradenitis suppurativa, intertrigo, eczematous dermatitis, pyoderma gangrenosum, erythema nodosum, cellulitis, and sexually transmitted infections. A detailed history, physical examination, and biopsy are essential for differentiation, they wrote.

References

  1. McKay GE, Liu L, Shaw KSS, et al. Pediatric cutaneous Crohn disease: A case series of 89 patients and review. Pediatr Dermatol. Published online July 16, 2024. https://doi.org/10.1111/pde.15689
  2. National Center for Biotechnology Information. Cutaneous Crohn disease - StatPearls - NCBI Bookshelf. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470311/#:~:text=Generally%2C%20the%20lesions%20are%20plaques,extremities%2C%20face%2C%20and%20genitalia. Accessed July 18, 2024.
  3. Parks AG, Morson BC, Pegum JS. Crohn's disease with cutaneous involvement. Proc R Soc Med. 1965; 58(4): 241-242.
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