Dissecting Cellulitis of the Scalp Successfully Treated with a Combination of Ixekizumab and Tofacitinib

A 28-year-old man presented with multiple painful nodules and alopecia patches on the scalp for 3 years (Figure 1A). Previous treatment included oral and topical antibiotics and traditional Chinese medicine. Physical examination showed fluctuant subcutaneous nodules with patches of alopecia on the vertex, with some of the nodules evolve to abscesses and sinus tracts. And the body mass index of the patient is 32.8. His baseline laboratory examination showed elevated white blood cell count, hyperlipidemia and fatty liver. He also had a history of severe acne (healed after puberty) and smoking. Biopsy of the scalp lesion demonstrated a mixed dermal infiltrate with predominant lymphocytes and numerous plasma cells, and focal areas with neutrophils and multinucleated giant cells. Chronic inflammatory cells extend into hair follicles and subcutaneous tissues, with significant folliculitis and abscess formation (Figure 1C and D). The diagnosis of dissecting cellulitis of the scalp (DCS) was made according to the clinical and histopathologic manifestation. The patient was prescribed 160 mg ixekizumab for the first dose, followed by 80 mg every 2 weeks, combined with oral 10 mg tofacitinib per day, 200 mg doxycycline per day for 10 days then transferred to 20 mg isotretinoin per day. After 3 months, his scalp abscesses and exudate were significantly regressed, and new hair grew. The white blood cells dropped below the normal value. Isotretinoin was stopped, and ixekizumab was reduced to 80 mg per 4 weeks. After 10 months’ treatment, most of the nodules disappeared and the dermatology life quality index decreased from 18 to 6 (Figure 1B). No serious adverse events were reported.

Figure 1 The clinical and histopathologic manifestations for dissecting cellulitis of the scalp. The lesions before treatment (A) and the lesions after 10-month-treatment (B) Histopathologic manifestations, hematoxylin-eosin staining: 1.25X (C), black arrow shows sinus tract; 40X (D), back arrows show multinucleated giant cells.

DCS is a rare chronic inflammatory skin disease characterized by multiple painful nodules, abscesses, and sinus tracts on the scalp that slowly progress to primary cicatricial alopecia (PCA) and keloids.¹ Trichoscopy shows yellow dots, black dots and exclamation mark hairs in the early stage, similar to alopecia areata. As the disease progresses, follicles become fibrotic and loss of follicular openings appear. The differential diagnosis includes other scalp nodules or patches of alopecia disease, including mycosis fungoides, tinea capitis and folliculitis decalvans. Early diagnosis and effective treatment are essential to prevent DCS to keloids. The basic treatment, oral antibiotics and isotretinoin, usually achieved partial or complete remission, but frequent relapses after discontinuation.² Most of the novel therapies for DCS are based on the experience of hidradenitis suppurativa (HS), another disease in the same spectrum, including biologics targeting tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-36, IL-1, and small molecules Janus kinase inhibitors (JAKi).³

The TNF-αinhibitor adalimumab and the IL-17 inhibitor secukinumab are the only two biologics approved for HS, but have shown only moderate efficacy, and there are still one-quarter to one-third of patients do not respond to the treatment.^4,5 Thus, experts recommend a combination between biologics and other biologics or small molecules to widely cover the pathological processes and rapidly control the inflammation response.⁶ Drugs targeting the IL-17 and JAK pathways are the most advanced in both ongoing and completed Phase 3 studies for HS, the combination of IL-17 inhibitors and JAKi in the treatment of severe HS or DCS is expected to produce a more promising deep response. To the best of our knowledge, two cases of secukinumab^7,8 and one case of upadacitinib have been reported for the treatment of severe DCS.⁹ We are the first case of DCS treated with the combination of IL-17 inhibitors and JAKi, but there was already case report of a Chinese boy who was successfully treated with adalimumab and baricitinib.¹⁰ IL-17 inhibitors have demonstrated superior efficacy and safety profile in the treatment of psoriasis compared to TNF-αinhibitors, giving us more confidence in their off-label use for other inflammatory skin conditions.

Although the combination of biologics and JAKi were suspected to be associated with a higher risk of adverse events, like infections, tumors,¹¹ our case suggests that with regular follow-up, satisfactory clinical efficacy can be obtained within a controllable range. This case provides new experience for the management of severe DCS, but larger randomized controlled trials in the future are needed to provide more reliable evidence for the treatment strategy for this disruptive disease.