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  • Writer's pictureIvan Bristow

Necrobiosis Lipoidica and JAK inhibitors

Necrobiosis Lipoidica (NL) is a skin condition commonly associated with diabetes mellitus (referred to as Necrobiosis Lipoidica Diabeticorum [NLD]).

Necrobiosis Lipoidica affecting the shin

Image: Primary Dermatology Society (Click here)

It characteristically appears as waxy brown-yellow, atrophic plaques on the anterior of the shins but has been reported on the thighs, abdomen, back, breast, head and forearms (1). Ulceration of the lesion is not uncommon often with associated pain. The condition affects females 3 times more often than males. Rare in childhood, the condition mainly affects adults. Although associated with diabetes, the prevalence is unknown, particularly in non-diabetic populations.

A review of 328 cases at one centre in the USA (2) reported confirmed 86% were female with an average age of 46 years. Diabetic status was known in 298 patients with 56% reporting diabetes (34% type 2, 22% type 1). In this diabetes group, 91% of lesions were present on the shins and showed as an annular (64%), red (79%), yellow (61%) and atrophic (78%) plaque with telangiectasia (62%). Atrophy was more common in patients with type 1 diabetes and telangiectasia were more common in patient with diabetes.


Reports of successful treatments for NLD are in short supply. A systematic review investigating the relationship between glycaemic control and NLD in patient with diabetes summarised 10 papers. In the series, 13 of 24 patients reported resolution of lesions following various measures to improve glycaemic control such as diet, insulin regimen and pancreatic transplantation (3). In younger patients, guidance is lacking and so a another review systematically analysed papers from 1990 onwards which focussed on therapy for younger patients. There were 55 therapeutic regimens reported with only 9 reporting complete clearance. Treatments typically involved topical steroids, tacrolimus (calcineurin inhibitors), local wound agents such as honey, hyaluronic acid, photodynamic therapy, and skin substitutes. Newer drug treatments may offer more hope. The use of IL-17 inhibitors (secukinumab) has shown some early positive results in a small cohort of female patients with pretibial lesions (4) but larger studies are needed to corroborate these findings.

JAK Inhibitors

A promising class of drug which has shown some benefit is the Janus Kinase (JAK) inhibitors. The group includes agents such as tofacitinib (Xeljanz®), abrocitinib (Cibinqo®), baricitinib (Olumiant®), upadacitinib (Rinvoq®), ruxolitinib (Jakovi®) and filgotinib (Jyseleca®) which are used to treat chronic inflammatory disorders such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis and ulcerative colitis. They work by blocking the receptors sensitive to pro-inflammatory cytokines on immune cells. Three case studies have been published (5, 6, 7). In one case a 48 year old woman who had extensive pre-tibial lesions responded rapidly to oral tofacitinib (10 mgs daily) (7). The authors postulate that the drug blocks activity of pro-inflammatory molecules (IL-6, IL-12 and IL-23) allowing healing to occur. In a second case a 25 year old with a seven year history of NLD, underwent 6 weeks of tofacitinib and topical corticosteroids which resolved the ulceration (6). A third patient with multiple areas of NLD showed rapid clearance following administration of ruxolitinib, 10 mg, orally twice daily.

How do JAK inhibitors work in NLD?

The idea that JAK inhibitors may hold the key to managing certain inflammatory disorders has been discussed (8) including sarcoidosis, granuloma annulare and NLD. All three conditions are linked as they feature granulomas in affected tissues.

A granuloma is a mass of immune cells of predominantly macrophages in response to chronic inflammation. In NLD, macrophages can be seen aggregating as a palisade around altered collagen in the skin. In granulomatous disorders, macrophages are activated by an unknown trigger. During granulomatous inflammation cytokines are produced by activated macrophages and T Helper (CD4+) cells. This release from each cell stimulates the other (known as “cross-talk”) to further release more cytokines producing a steady, self-sustaining loop of inflammation (8) – see figure below.

Image showing cross talk between macrophage and T helper cell creating chronic inflammatory state. Image from Wang et al., (2020) reproduced under the creative commons licence.

The inflammation occurs as released cytokines bind to specific receptors on each of the target cells using the JAK-STAT pathway to transmit the signal into the cell to elicit a response. JAK inhibitors are orally administered drugs which break the transmission of inflammatory signals, and thus reduce further cytokine release and quelling inflammation. This allows healing to occur.

Implications for treatment

Reports to date on the use of JAK inhibitors in NLD have been limited but show some promise in treating an otherwise stubborn condition. An additional consideration is that the drugs although potentially effective, have side effects. Recent UK guidance from the Medicines and Health Regulatory Authority (MHRA), suggested that JAK inhibitors should not be used in over 65's, those at increased risk of major cardiovascular problems; those who smoke or have done for a long time in the past; or those at an increased risk of cancer, unless no other option was available (Click Here). More research is needed to unravel the cytokine story and potentially develop more targeted drugs specific to individual diseases.


1. Schiefer-Niederkorn A, Sadoghi B, Binder B. Necrobiosis lipoidica in childhood: a review of literature with emphasis on therapy. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2023; early view

2. Severson KJ, Costello CM, Brumfiel CM, Patel MH, Butterfield RJ, Nelson SA, et al. Clinical and Morphological Features of Necrobiosis Lipoidica. J Am Acad Dermatol. 2021.

3. Mistry BD, Alavi A, Ali S, Mistry N. A systematic review of the relationship between glycemic control and necrobiosis lipoidica diabeticorum in patients with diabetes mellitus. Int J Dermatol. 2017;56(12):1319-27.

4. Gibson RS, Salian P, Beckles A, Stavert R, Tahan S, Kimball AB, et al. Treatment of necrobiosis lipoidica with secukinumab (Cosentyx): a case series. Int J Dermatol. 2023; early view.

5. Lee JJ, English JC, III. Improvement in Ulcerative Necrobiosis Lipoidica After Janus Kinase–Inhibitor Therapy for Polycythemia Vera. JAMA Dermatology. 2018;154(6):733-4.

6. Damsky W, Singh K, Galan A, King B. Treatment of necrobiosis lipoidica with combination Janus kinase inhibition and intralesional corticosteroid. JAAD case reports. 2020;6(2):133-5.

7. Janßen S, Jansen TM. Ulcerated necrobiosis lipoidica successfully treated with tofacitinib. Int J Dermatol. 2022;61(6):739-41.

8. Wang A, Singh K, Ibrahim W, King B, Damsky W. The Promise of JAK Inhibitors for Treatment of Sarcoidosis and Other Inflammatory Disorders with Macrophage Activation: A Review of the Literature. Yale J Biol Med. 2020;93(1):187-95.

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