Knuckle Pads Successfully Treated with 2% Crisaborole Ointment Combined with Triamcinolone Acetonide and Neomycin Plaster: A Case Report

Abstract

Knuckle pads (KPs) are benign hyperkeratotic fibrous thickening skin disorder characterized by nodules or plaques located on the extensor surface of the joints. However, there are no specific treatments for KPs so far. Here, we reported a case of KPs successfully treated with 2% crisaborole ointment combined with triamcinolone acetonide and neomycin plaster. This combined therapy might be a new therapeutic option for KPs.

Keywords:

• knuckle pads
• crisaborole
• PDE-4 inhibitors
• primary
• emerging therapy

Introduction

Knuckle pads (KPs) are usually presented with nodules or plaques located on the extensor surface of the joint, which are caused by fibrous thickening of the skin.^1,2 The diagnosis of knuckle pads mainly depends on clinical presentation, and it can be confirmed by ultrasound imaging, thus limiting the risk of misdiagnosis.^1–3 Histopathologically, patients usually present with acanthosis with hyperkeratosis, connective tissue hyperplasia, and collagen fiber hypertrophy.^2,4 The benign skin lesions do not affect joint movement with no particular symptoms and generally do not require treatment. However, in many patients KPs are badly tolerated due to cosmetic reasons, and unfortunately many of the conventional treatments including intralesional corticosteroid injection and surgery are usually ineffective as well as bring a series of traumatic problems and side effects.^5–7 Despite this, some new potential therapies are emerging.^2,7–10 Here, we reported a case of KPs successfully treated with 2% crisaborole ointment combined with triamcinolone acetonide and neomycin plaster.

Case Report

A 45-year-old man presented to our hospital with a six-year history of asymptomatic thick plaques on the extensor aspect of both knuckles and ankles (Figures 1A, 2A and B) that had been histopathologically diagnosed as knuckle pads (Figure 3), denying any repetitive scratching, rubbing to this area or a family history. He had previously undergone intralesional steroid injections several times and received ultrahigh potency topical corticosteroid like clobetasol and flumethasone for three years but with poor efficacy. Several depigmentary rings were seen around the plaques due to long-term use of the glucocorticoid (Figure 1A). Given the poor efficacy of the previous treatments, the patient agreed to receive a new treatment option. He was treated with triamcinolone acetonide and neomycin plaster quaque nocte, removed the plaster on another day then applied 2% crisaborole ointment twice daily. After two-week treatment, we could observe a remarkable improvement – the skin lesions became significantly thinner, and there were no adverse effects. Improvement was sustained at 2-month follow-up with enhanced repigmentation of the depigmentary rings around the plaques (Figures 1B, 2C and D).

Figure 1 Plaques in extensor interphalangeal joints of both hands before and after treatment. (A) Plaques in extensor interphalangeal joints of both hands before treatment. (B) Two months after treatment.

Figure 2 Plaques on both ankles before and after treatment. (A and B) Plaques on both ankles before treatment. (C and D) Two months after treatment.

Figure 3 Histopathology of a plaque on the hand knuckle. (A) Hematoxylin-eosin (H&E) staining shows compact hyperkeratosis, epidermal hyperplasia, elongation of rete ridges and subdermal fibrous tissue hyperplasia (original magnification: 20×). (B) H&E, at a higher magnification of Figure 3A (original magnification: 40x).

Discussion

Although most Knuckle pads (KPs) do not require treatment, some patients desire intervention for cosmetic purposes.² Traditional therapies such as topical corticosteroids, keratolytics, and intralesional corticosteroid injection have a limited impact. Some reports have indicated successful application of intralesional 5-fluorouracil injection but it shows toxicity including gastrointestinal discomfort and bone marrow suppression.⁸ Recently, some treatments such as laser, high-dose salicylic acid combined with 40% urea cream and the combination of topical cantharidin-podophylotoxin-salicylic acid showed a successful therapeutic strategy for KPs.^2,7,9 However, the invasive nature of laser therapy and the drug-induced skin irritation cannot be avoided. Non-traumatic and low-side effect treatment for KPs are eagerly developed. In addition, a recent study mentioned that a medical silicone gel sheet has been used to effectively treat a case of pseudo-knuckle pads.¹⁰ The therapeutic method is simple, non-invasive and is more receptive for patients. Nonetheless, it needs to be applied to the lesion for most of the day, which may cause the peeling of silicone gel patch owing to daily joint movement.

Crisaborole, a topical phosphodiesterase-4 (PDE-4) inhibitor, shows an anti-inflammatory effect by reducing cyclic adenosine monophosphate (cAMP) degradations.¹¹ However, it is currently only approved for the treatment of mild-to-moderate atopic dermatitis in adults and children greater than two years of age in China.¹² Several studies have indicated that crisaborole has good therapeutic effects on some other inflammatory dermatoses such as psoriasis and vitiligo¹³ as well as hypertrophic lesions like neurodermatitis.¹⁴ Therefore, crisaborole may have a great potential for other hypertrophic lesions. Previous studies showed that PDE-4 inhibitors could block keratinocyte proliferation as well as fibroblast chemotaxis by up-regulating cAMP,¹⁵ which controls cell proliferation, differentiation, and migration.¹⁶ Crisaborole is a boron-containing tiny molecule ointment that can effectively penetrate the skin and it also contains vaseline which can soften the corneum. Based on the possible mechanisms of PDE-4 inhibitors and the special drug structure of crisaborole itself, we speculated that crisaborole may treat KPs well through inhibiting hyperkeratosis and fibroblast chemotaxis.

Among triamcinolone acetonide and neomycin plaster, triamcinolone acetonide has a strong anti-inflammatory effect.¹⁷ The plaster is often used as a patch that can offer an occlusive environment, softening the skin lesion, and improve medication permeability.¹⁸

In this case, we observed a remarkable therapeutic effect and crisaborole was well tolerated in KP lesions. The combination with the plaster can simultaneously relieve skin depigmentation and may significantly shorten the time of the high potency corticosteroid use in the subsequent maintenance therapy. It is convenient and simple, avoiding the risk of traumatic and painful caused by local injection and surgery, and may be a beneficial therapeutic option for patients who wish to minimize medication side effects, but this still requires controlled trials with a larger sample size and to set up single medication regimens to further evaluate the efficacy of crisaborole as a treatment for KPs.

Conclusion

Knuckle pads (KPs) are benign skin disorder with only cosmetic concerns but for which no specific therapeutic approach exists so far. Two percent crisaborole ointment combined with triamcinolone acetonide and neomycin plaster may be expected to be a novel treatment option for KPs that shows convenience and good tolerance.

Consent Statement

The patient had given written informed consent for the publication of the clinical details and accompanying images. Institutional approval was not required to publish the case details.

Disclosure

Yimin Liang and Jingyao Liang are co-first authors for this study. The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the Guangzhou Health Science and Technology Pro-ject (grant number 20211A011067) and the Science and Technology Planning Project of Guangzhou (grant number 201904010082).