Blocking IL-17/IL-23: A new Option for Dissecting Cellulitis

TH17 Pathway Inhibitors Increasingly Showing Benefit in Dissecting Cellulitis

Dissecting cellulitis (DSC) is neutrophilic scarring alopecia that often affects young patients. It has a similar pathogenesis to hidradenitis suppurativa (HS) - a condition with draining sinuses and ‘boils’ in the armpits and groin. Together, dissecting cellulitis, hidradenitis suppurativa, acne conglobata and pilonidal cysts are referred to as the “follicular occlusion tetrad.” All of these conditions share in common features of abnormal keratinization, follicular wall collapse and subsequent acute neutrophilic and chronic granulomatous inflammation and sometimes secondary infection.

Given the similarities of HS to DSC, researchers often look to novel treatments from the HS research world to bring to the DSC treatment algorithm.

Studies of HS have shown increased levels of IL-23 within macrophages in lesional dermis, thus it was speculated that IL-23 may also be implicated in the pathogenesis of DSC.

Four recent studies suggest that the TH17 pathway may be implicated in the pathogenesis of DSC and that drugs targeting IL-17 and IL-23 may be helpful treatments.

Muzumdar S et al. 2020

Muzumdar and colleagues reported a male with refractory DSC with concurrent hidradenitis suppurativa, who had failed treatment with multiple topical and systemic therapies. After receiving the IL-23 inhibitor guselkumab (Tremfya) 100 mg subcutaneously every 8 weeks, the patient exhibited marked improvement, with normalization of symptoms and signs.

De Bedout V et al 2021

In 2021, De Bedout and colleagues reported a patient with refractory DSC who responded to Secukinumab (Cosentyx), a human monoclonal anti–interleukin (IL)-17A antibody approved for the treatment of moderate to severe plaque psoriasis.

The patient was a 63-year-old male with dissecting cellulitis of his occipital scalp for more than four years. The patient had previously failed multiple treatments including doxycycline, trimethoprim-sulfamethoxazole, clindamycin, rifampin, adalimumab and isotretinoin. The patient was finally started on oral dapsone 12.5 mg daily with gradual increase to 50 mg daily and concomitant intralesional triamcinolone 10 mg/cc. After three months, there was little symptomatic improvement, and the patient noted weekly flares. Treatment with secukinumab 150 mg subcutaneous monthly injections after 4 weekly loading doses was initiated concomitantly with dapsone 50 mg daily. The patient injected 6 weekly doses in error and then continued for two more months of single injection each month. In total, the patient injected 8 injections of 150 mg over three months. The patient could not receive additional doses of medication due to lack of insurance coverage. Following one-month therapy, the patient’s drainage and pain completely stopped, and his nodules began regressing for the first time in six years.

Babalola et al, 2022

Babalola present a patient with DSC responding well to Risankizumab, a humanized monoclonal antibody targeting interleukin 23A. The drug goes by the trade name Skyrizi.

The patient was a 65-year-old African American male presented to the dermatology clinic with a 13-year history of DSC. The patient previously failed or had minimal response to topical clindamycin, doxycycline 100mg BID, intermittent intralesional triamcinolone, chlorhexidine gluconate, fluocinonide, and isotretinoin 30mg BID

Awad and Sinclair, 2022

Awad and Sinclair present the most recent case of DSC responding to an IL-23 inhibitor. Specifically, they present a case of DCS successfully treated with tildrakizumab, an anti-interleukin-23 (IL-23) monoclonal antibody. The drug goes by the name Ilumya in the US and Ilumetri in the European Union.

The patient was a 28 year old male who failed initial treatment with isotretinoin 20mg, erythromycin 500mg and intralesional triamcinolone injections. Two doses of subcutaneous injection of tildrakizumab 4weeks apart produced a significant reduction in the number and severity of pustules and alleviated scalp tenderness along with hair regrowth in the areas of alopecia.

Comment

The exact reasons why Il-23 inhibitors are so successful in DSC is not clear. It is proposed that increasing amounts of IL-23 and TNF-alpha are increased from dendritic cells and macrophages. Il23 can then stimulate TH17 cells. It could be that the TH17 pathway plays a role in DSC.

TH17 cells are a newly discovered type of T helper cell that secretes IL-17. The development and maintenance of TH17 cells has been linked to IL-23 , a key initiating cytokine in the development of autoimmunity. Therefore this pathway is often referred to as the IL-17/TH17 pathway. IL-23 binds to and signals through its heterodimeric receptor complex composed of IL-12Rβ1 and IL-23R subunits. The IL-12Rβ1 and IL-23R chains lack any sort of intrinsic signaling activity.Rather, they are associated with intracellular proteins to induce downstream signaling. IL-12Rβ1 binds to the Jak family member, Tyk2. IL-23R associates with Jak2.

IL-23 promotes the expansion of Th17 T helper cells, which are characterized by the production of IL-17A and other related proinflammatory cytokines.

REFERENCE

Awad A and Sinclair R. Treatment of dissecting cellulitis of the scalp with Tildrakizumab. Australas J Dermatol 2022 May 4.

Babalola et al. Refractory Dissecting Cellulitis of the Scalp Treated With Risankizumab. J Drugs Dermatol. 2022 Mar 1;21(3):313-314.

Muzumdar S et al. Treatment of refractory dissecting cellulitis of the scalp with guselkumab: Case report. Journal of Dermatology and Dermatologic Surgery; 2020; 24(1): 52-53.

De Bedout V et al. Treatment Dissecting Cellulitis of the Scalp With Secukinumab. J Drugs Dermatol . 2021 Jul 1;20(7):776-777.