Topical Corticosteroid Powder for Peristomal Pyoderma Gangrenosum: A Systematic Review

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PG is a neutrophilic dermatosis that typically presents as rapidly progressive, painful ulcerative lesions with irregular, violaceous, and undermining borders.^1-3 PG is associated with systemic diseases—often IBD, arthritis, and hematological and solid malignancies—in more than half of PG cases (56.8%).⁴ PG has several clinical variants, including classic (ulcerative), bullous, pustular, vegetative (superficial granulomatous), and peristomal subtypes.¹ Current treatments for PG involve topical and systemic approaches such as topical corticosteroids, calcineurin inhibitors, systemic corticosteroids, cyclosporine, and biologics. However, there is no gold standard treatment.¹

A practical approach to the local management of PG has been proposed: PG-TIME.⁵ The PG-TIME approach involves debridement of devitalized tissue with hydrogel or collagenase; infection control with antiseptic dressings; inflammation control with topical corticosteroids, tacrolimus, or compression bandage; and moisture control with absorbent dressings for management of the inflammatory phase of PG. In addition, bioactive dressings or allografts, epidermal grafts, and skin substitutes are required to promote epithelial edge enhancement in the noninflammatory healing phase.⁵

The peristomal subtype of PG occurs as a complication of surgical ileostomy or colostomy placement, typically in individuals with IBD. PPG is uncommon, accounting for approximately 15% of PG cases.⁶ In 1975, Barker et al⁷ described PPG as a pathergy response to skin irritation from feces or skin trauma from adhesive removal from an ostomy appliance. Management of PPG often involves a combination of topical and systemic therapies along with ostomy care.

Although corticosteroids can be used topically in the form of a cream, ointment, solution, spray, or gel, these formulations tend either to inhibit pouch adhesion due to the vehicle lipid content or to be painful due to isopropyl alcohol, both of which pose a challenge in the management of PPG. Topical use of powder from crushed corticosteroid tablets or budesonide capsules is an approach for the treatment of PPG that can be mixed directly with ostomy adhesive powder, ensures adequate adhesion, and minimizes pain. The authors of the current study conducted a systematic review to evaluate the safety and effectiveness of the topical use of crushed corticosteroid tablets or powder from budesonide capsules in the management of PPG.

Protocol and search strategy

The PRISMA reporting guidelines were followed for this systematic review. The review was registered with PROSPERO (CRD42023474390).

A systematic literature search of 3 databases—PubMed, Scopus, and Embase—from inception to October 23, 2023, was performed using the medical subject headings and keywords "crushed", "powdered", "tablets", "capsules", and "pyoderma gangrenosum." Any studies including the use of corticosteroid powder for the management of PPG were considered, including published abstracts, with no language or publication date restrictions.

Eligibility criteria and screening

Two reviewers (M.K., B.H.K.) independently screened the abstracts of a total of 35 studies for inclusion using Covidence systematic review software (Veritas Health Innovation), followed by a full-text review of the qualifying studies. Five studies met the selection criteria.^2,3,8-10 The reference lists of all the included studies were manually reviewed for any additional studies not identified in the initial search.

Data extraction and quality assessment

Data on the study characteristics, publication year, study participants, disease characteristics, treatment regimen, and outcomes were extracted. Two reviewers independently extracted data and assessed studies for RoB. Any disagreements were resolved through discussion. JBI critical appraisal lists for quality assessment of case reports and case series were used for critical quality appraisal.¹¹ All 5 studies were included in the qualitative data synthesis.

Search and study characteristics

The search of databases retrieved 54 results. After eliminating duplicates, the abstracts of 35 citations were screened for inclusion. The PRISMA flow diagram illustrates the search details and screening process (Figure). Five studies—3 case reports and 2 case series—fulfilled the eligibility criteria and were included in the analysis. Included studies, treatment protocols used, and outcomes are noted in Table 1. Topical powder from crushed corticosteroid tablets was used for PPG treatment in 12 cases, with powder from budesonide capsules used in only 1 case.

RoB assessment

Possible answers to JBI checklists were "yes" (indicating low RoB), "no" (indicating high RoB), "unclear," and "not applicable." The following cutoffs were used for the assessment: low RoB if greater than or equal to 70% of answers were "yes"; moderate RoB if 50% to 69% of answers were "yes"; and high RoB if less than 50% of answers were "yes." Two of the 3 case reports had a low RoB (100%, 8/8 "yes"answers),^8,9 and the conference abstract report had a moderate RoB (50%, 4/8 "yes" answers).² Both case series had a low RoB (70%, 7/10 "yes" answers)^3,10 (Table 2, Table 3).

Demographic and clinical characteristics

A total of 13 patients with PPG underwent different treatment protocols using powder from crushed prednisolone tablets and budesonide capsules, including 10 females (76.9%) and 3 males (23.1%) with a median age of 66 years (range, 36–82 years).

Analysis of the available data indicates that 5 patients underwent surgeries resulting in a stoma construction because of underlying IBD (38.5%) (mostly Crohn disease [30.8%], with 1 case of ulcerative colitis [7.7%]). Other underlying causes were rectal cancer (23.1%), interstitial cystitis (15.4%), diverticulitis (7.7%), and short gut syndrome (7.7%). Information on the ostomy type was available for 7 of 13 cases (53.8%). In these 7 cases, the ostomy type was predominantly colostomy (57.1%), followed by ileostomy (28.6%) and urostomy (14.3%).

The rationale for topical corticosteroid powder use

The primary reasons for using the topical corticosteroid powder were the failure of first- and second-line treatments of PPG, side effects of systemic therapies, and/or interference with the pouch adhesion. Corticosteroid powder was tried in cases in which other topical therapies (betamethasone dipropionate, tacrolimus, dapsone), intralesional corticosteroid injections, and systemic treatments (corticosteroids, infliximab, mycophenolate mofetil) had been unsuccessful. However, the reasons for use of topical corticosteroid powder were not reported for 6 of 7 cases in Pearson et al¹⁰ and 1 of 3 cases in DeMartyn et al.³

Clinical outcomes and time to improvement

Different treatment protocols using powder from crushed prednisolone/prednisone tablets and budesonide capsules were used (Table 1). Among the studies using crushed corticosteroid tablets, 2 studies used prednisone^3,9 and 2 others used the active form of the drug, prednisolone.^2,10 The doses of corticosteroid tablets used for the treatment of PPG in different studies were variable, ranging from 1 mg^2,3 to 5 mg.^9,10 The number of tablets used ranged from 1 tablet^2,3,10 to 4 tablets⁹ per topical use depending on the wound size. In the sole patient treated with budenoside, a single budesonide 3 mg capsule was used per application. Treatment outcomes were reported as a decrease in pain, improved pouch adherence, and healing of PPG lesions in 12 of 13 patients (92.3%).

Improvement in pain and pouch adherence was seen within days of starting the treatment, with a maximum of 65 days to improvement. Significant healing of the lesions was reported within as early as 10 days of starting treatment. The time to complete healing was variable, ranging from 3 weeks to 1 year. Only 1 patient (case 6 in Pearson et al¹⁰) showed no response, and her stoma was reversed before healing of the ulcerations was achieved.

Recurrence after topical corticosteroid powder use was reported in 2 of 13 cases, with 1 case of peristomal hernia (case 3 in DeMartyn et al³), and 1 case in which the lesions healed using the same treatment regimen as for the first occurrence (case 4 in Pearson et al¹⁰).

Concomitant systemic treatment

Twelve of 13 cases were treated with the topical corticosteroid powder alone. Concomitant treatment with oral prednisolone was administered in only 1 case (case 1 in Pearson et al¹⁰).

The current review identified 5 studies comprising 13 cases treated with topical corticosteroid powder in the management of PPG. Different treatment protocols were followed for the topical use of crushed corticosteroid tablets (Table 1), and only 1 report described the use of powder from budesonide capsules. PPG lesions healed in 12 of 13 cases (92.3%). Other reported outcomes in these cases were reduction in pain and improvement of pouch adherence.

In line with the existing literature, in the current study IBD (predominantly Crohn disease) was the most common underlying disease resulting in PPG; IBD was present in 5 of 13 cases (38.5%), out of which 4 (80%) had Crohn disease. In a systematic review of 335 patients with PPG, 81% of patients with underlying systemic disease had concomitant IBD (50% of these patients had Crohn disease and 31% had ulcerative colitis) PPG was seen more frequently after ileostomies (78%) than colostomies (16%).¹²

Management of PPG includes a combination of topical and systemic immunosuppression, wound care compatible with an ostomy pouching system, and pain control. Ostomy pouch adhesion and fit are imperative to maintain a complete seal in order to prevent leakage of effluent and worsening of PPG. Topical steroids in the form of gels, creams, ointments, sprays, and solutions are not considered to be very effective in the management of PPG because they interfere with pouch adhesion and may cause pain due to their alcohol content. Although corticosteroids can be administered as intralesional injections, they are painful, not uniformly effective, and only dosed intermittently.

When prednisolone tablet powder is mixed with a hydrocolloid powder, it forms a gel that acts as a barrier to bacterial infection and preserves the moisture in the wound bed, thus promoting wound healing.^13,14 It has been hypothesized that the hydrocolloid powder acts as a vehicle that facilitates dissolution and release of the corticosteroid, resulting in continuous bioavailability of the drug at the wound location while allowing the pouch to adhere to the peristomal skin.¹⁰

Topical use of crushed prednisolone tablets for the management of PPG was first reported by DeMartyn et al,³ who used a mixture of crushed prednisone 1 mg tablet and hydrocolloid powder in 3 patients. Use of this mixture resulted in rapid and complete healing of PPG lesions in all 3 cases, with an improved ability to maintain pouch adhesion for 3 days as well as a reduction in pain. There were no systemic complications. However, 1 patient with a peristomal hernia had a recurrence of PPG lesions. Although prednisone was used in this case, the authors of the current study suspect it is not the optimal corticosteroid for topical application as a prodrug requiring methylation in the liver for optimal effect.

In a different prospective study, 7 patients used a crushed oral prednisolone 5 mg tablet mixed with a stoma adhesive powder comprising 3 hydrocolloid polymers in a 1:1 ratio over the PPG lesions, resulting in decreased pain, improved pouch adherence, and wound healing, with recurrence in only 1 case.¹⁰ The authors of that article hypothesized that hydrocolloid powder acted as a vehicle for the continuous bioavailability of prednisolone in the form of crushed tablets at the inflammation site, resulting in improved healing in their patients.

The powder from budesonide capsules reportedly has similar clinical benefits when used topically over PPG lesions, and these capsules are US FDA-approved for IBD.⁸ Capsules may have some advantage in the ability to simply open the capsule and further crush or apply the time-release granules.

In the studies included in this systematic review, the most common reason for using the topical corticosteroid powder was the failure of first- and second-line treatments for PPG. The advantage of avoiding systemic toxicities of the drugs and retaining the ability of pouch adherence with the use of topical corticosteroid powder also played a positive role in decision-making. None of the included studies reported any side effects.

This study was limited by its retrospective nature, the existence of only a few reported cases, and the low quality of available evidence of the included studies.

The findings of the current systematic review suggest that topical use of powder from crushed corticosteroid tablets or budesonide capsules is an efficacious treatment strategy that allows improved pouch adherence. However, current evidence is limited because of the small number of cases reported and the low quality of the evidence. Future randomized clinical trials involving a larger number of patients are required to evaluate the effectiveness of topical corticosteroid powder as an alternative to other topical steroid formulations for the treatment of PPG.

Authors: Manjit Kaur, MBBS, MD; and Benjamin H. Kaffenberger, MD, MS

Affiliation: Department of Dermatology, The Ohio State University Wexner Medical Center, Columbus, OH 

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Manjit Kaur, MBBS, MD; The Ohio State University Wexner Medical Center, 1328 Dublin Road, Suite 100, Columbus, OH 43215; Manjit.kaur@osumc.edu

Manuscript Accepted: July 9, 2024