Apremilast for Acrodermatitis Continua of Hallopeau: Report of Two Cases and Review of the Literature

ABSTRACT

Acrodermatitis continua of Hallopeau (ACH) is a rare, localized variant of pustular psoriasis characterized by painful paronychia. It primarily affects the distal phalanges and is frequently refractory to standard topical treatments. Establishing an optimal systemic therapy is clinically challenging, particularly for women of childbearing age, given the teratogenicity of retinoids and methotrexate, as well as the adverse effect profiles associated with cyclosporine. Herein, we present two cases of Japanese women in their 30s with recalcitrant ACH who were treated with apremilast. In Case 1, erythema and pain resolved within two months. In Case 2, while skin lesions responded favorably, persistent joint symptoms and headaches necessitated a switch to risankizumab. To evaluate broader utility, we analyzed 10 ACH cases (our two and eight from literature). Clinical efficacy for skin lesions was observed in 90% (9/10), and the response rate for joint pain reached 80% (4/5), with a median response time of 2 months. Notably, apremilast also demonstrated a favorable safety profile even with comorbidities like viral hepatitis. Although 30% of patients experienced mild adverse events (e.g., nausea, headache), the medication was generally well‐tolerated. While this review is limited by potential publication bias inherent to case reports, and treatment responses vary, with one study showing limited efficacy, apremilast may be considered among systemic treatment options. Given its non‐teratogenic nature and cost‐effectiveness compared to biologics, we recommend apremilast as one of the first‐line systemic treatment options for ACH patients resistant to topical regimens, especially those of childbearing potential.

1. Introduction

Acrodermatitis continua of Hallopeau (ACH) is a localized form of pustular psoriasis preferentially affecting the fingers and toes [1]. It frequently manifests as periungual erythema or diffuse erythema with small pustules on the distal phalanges, accompanied by nail deformity. On rare occasions, it may progress to generalized involvement with systemic symptoms, mimicking generalized pustular psoriasis [2]. Pathogenesis likely involves the IL‐36 axis [3].

The treatment strategy for ACH is not well established. Although therapeutic options include topical corticosteroids or calcineurin inhibitors, and systemic agents such as retinoids, cyclosporine, low‐dose methotrexate, apremilast, biologics, and JAK inhibitors, there is limited clinical evidence to guide selection [1]. Furthermore, treatment selection is particularly challenging for women of childbearing potential due to the teratogenicity or adverse effect profiles of conventional systemic agents.

Herein, we present two cases of ACH treated with apremilast and review the literature to evaluate its position as a systemic treatment option.

2. Case Report

2.1. Case 1

In January 2023, a 31‐year‐old Japanese woman was referred to our hospital with a crusted, pustular erythema on her left thumb (Figure 1a,b). In August 2022, she noticed small pustules on her left thumb tip. Two months later, pain developed in the affected skin. She had been treated with topical corticosteroids, systemic antibiotics, and topical antibiotics, which resulted in a recalcitrant clinical course. Her current medications included oral contraceptives, which she had taken for 5 years. She was a never‐smoker. A diagnosis of ACH was made. Screening for focal infections revealed no dental abnormalities, although sinusitis was identified during an otolaryngological evaluation. She was treated with oral apremilast (30 mg twice a day). Within two months, the erythema and swelling had almost entirely subsided, with subsequent improvement in onycholysis and complete resolution of pain (Figure 1c,d). The patient has continued apremilast for 30 months without any adverse events.

FIGURE 1.

Clinical images of the two patients with ACH before and after apremilast treatment. Case 1: A 31‐year‐old Japanese woman. (a, b) Scaly erythema with pustulosis on the left thumb along with nail deformity. (c, d) Two years after the initiation of apremilast treatment, the erythema has completely resolved. Case 2. A 31‐year‐old Japanese woman. (e, f) Diffuse erythema on the right middle and ring fingers, accompanied by subungual pustulosis and swelling of the distal interphalangeal joints. (g, h) Two months after the initiation of apremilast treatment, residual scaling is noted on the digital pads of the distal phalanges, but the erythema and nail changes have significantly improved.

2.2. Case 2

A 31‐year‐old Japanese woman was referred to our hospital complaining of vesicles, subungual pustules and pain in her right middle and ring fingers (Figure 1e,f). Her medical history included allergic rhinitis and chronic urticaria. She had no history of smoking. In February 2024, she developed spontaneous swelling and erythema in the nail matrix of the affected fingers. By November 2024, she also experienced pain in the distal interphalangeal (DIP) joint of her left ring finger. In January 2025, she consulted a local clinic, but her condition remained refractory to oral antibiotics, topical corticosteroid, topical difamilast, and oral cyclosporine at a dose of 100 mg per day. She was referred to our department in February 2025. Given her joint symptoms, she was also evaluated by the Department of Rheumatology. While radiography and joint ultrasonography showed no abnormalities, laboratory testing revealed that matrix metalloproteinase‐3, C‐reactive protein, antinuclear antibody, and anti‐cyclic citrullinated peptide antibody were within normal limits. Following a diagnosis of ACH, she was treated with oral apremilast (30 mg twice a day). Two months after starting therapy, her erythema and swelling had significantly improved (Figure 1g,h), while the DIP joint pain persisted. Additionally, she developed headaches; therefore, in June 2025, she was started on risankizumab (150 mg at weeks 0 and 4, and every 12 weeks thereafter), which led to the improvement of her DIP joint pain.

3. Literature Review of Acrodermatitis Continua Treated with APREMILAST

To assess the efficacy and safety of apremilast monotherapy in patients with ACH, we performed a literature review using PubMed, which identified eight case reports [4, 5, 6, 7, 8, 9, 10, 11] and one case series study [12] published between January 2015 and December 2025. Patient data concerning age, gender, prior treatments, treatment outcomes, time to response, and adverse events are summarized in Table 1. One case series study was excluded from Table 1 because detailed individual patient data were unavailable.

TABLE 1.

Prior systemic treatments, efficacy, time to response and follow‐up period.

Age/sex	Dosage, mg/day	Prior systemic treatments	Efficacy		Time to response, months	Follow‐up, months	Reference (no.)
			(Skin)	(Joint pain)
42/F	N/A	ABK, PSL, VACV	No	—	—	4	Baron [4]
53/F	60	Isotretinoin, MTX, infliximab	Partial	—	2	N/A	Smirnova [5]
58/M	60	Antifungals	Excellent	—	1	N/A	Lanna [6]
62/M	N/A	MTX	Excellent	Excellent	3	N/A	Kurihara [7]
75/M	60	ABK, PSL, VACV	Excellent	Excellent	1	6	Calleja Algarra [8]
72/M	N/A	—	Excellent	—	4	4	Megna [9]
61/F	60	Acitretin, MTX	Excellent	Excellent	3	24	Fustà‐Novell [10]
58/M	60	ABK, antifungals, MTX, Cys, COLC	Excellent	Excellent	1	24	Eleftheria [11]
31/F	60	ABK	Excellent	—	2	35	Our cases
31/F	60	ABK, Cys	Partial	No	2	11

Abbreviations: ABK, systemic antibiotics; COLC, colchicine; Cys, cyclosporine; MTX, methotrexate; N/A, not applicable; PSL, prednisolone; VACV, valacyclovir.

Prior systemic treatments included antibiotics, valacyclovir, retinoids, cyclosporine, methotrexate, and prednisolone. One patient had been treated with infliximab before starting apremilast [5]. As summarized in Table 1, clinical efficacy for skin lesions was demonstrated in 9 of the 10 patients (90%), consisting of 7 (70%) with an excellent response and 2 (20%) with a partial response. Joint pain was present in 5 of the 10 patients (50%). Clinical efficacy for joint pain was demonstrated in 4 of the 5 patients (80%) who achieved an excellent response. The median times to response and follow‐up were 2 months (range, 1–4) and 11 months (range, 4–35), respectively. Comorbidities and adverse events are summarized in Table 2. Two patients (20%) discontinued apremilast due to adverse events.

TABLE 2.

Complications and treatment‐emergent adverse events.

Complications, n	3/10
Hypertension	2/10
Dyslipidemia	2/10
Chronic kidney disease	1/10
HCV antibody positive	1/10
Diabetes mellitus	1/10
Latent tuberculosis infection	1/10
Chronic HBV infection	1/10
Adverse events, n	3/10
Nausea	2/10
Vomiting	1/10
Anorexia	1/10
Diarrhea	1/10
Headache	1/10

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus.

4. Discussion

ACH is a chronic, relapsing inflammatory condition that primarily affects the distal phalanges [1]. The typical clinical presentation is characterized by persistent, painful paronychia and collections of sterile pustules on an erythematous base around the nail folds and within the nail bed [1]. ACH is usually limited to 2–3 digits, but multiple digits can be affected, even all 20 [1]. ACH is suspected to be a specific form of pustular psoriasis, but the relationship between the two diseases remains controversial. IL‐36 axis, mainly based on IL36RN mutations, underlie the pathogenesis of both diseases [3], although differences in clinical presentation and treatment response between the two conditions can be observed [13].

In general, topical strategies tend to show limited efficacy for ACH. Treatment options include non‐biologic drugs such as retinoids, cyclosporine, methotrexate, and apremilast, as well as biologics and JAK inhibitors [1]. In recent recommendations, non‐biologic drugs such as retinoids, cyclosporine, and methotrexate have been listed as first‐line therapeutic options for ACH [1]. Apremilast and biologics have been recommended as second‐line options. Because retinoids and methotrexate have teratogenic potential, their use should be avoided in female patients of childbearing age. Additionally, cyclosporine can cause high blood pressure and renal impairment. Its use may provide only a short‐term control of the disease. While biologic treatments offer excellent efficacy for ACH, their high cost remains a major drawback.

Apremilast is a phosphodiesterase 4 inhibitor that exerts disease‐modifying and anti‐inflammatory effects, primarily through innate immune responses. The broad anti‐inflammatory effect of apremilast yields potential efficacy for various skin diseases with a sufficient safety profile [14, 15]. In our two cases of ACH, apremilast demonstrated favorable efficacy for skin and nail lesions. The results of our literature review (Table 1) show the efficacy and safety of apremilast in treating patients with ACH. Given that the median time to response was 2 months, a 2‐month follow‐up evaluation is recommended to validate its efficacy after starting apremilast. While apremilast requires discontinuation during pregnancy, its non‐teratogenic profile allows for its use in women of childbearing potential. Additionally, it is suitable for use even in hepatitis virus carriers.

This study is limited by reporting bias, as it involves a pooled analysis of anecdotal case reports where positive outcomes are more likely to be published. One case series study [12] reported that only 1 of 8 patients (13%) achieved a partial response. Given the lack of prospective trials, the actual efficacy rate might differ from our findings. However, the extreme rarity of ACH hinders the feasibility of randomized controlled trials. Thus, the accumulation of case series remains a vital step until more robust evidence can be established.

In conclusion, we recommend apremilast as a valuable systemic therapy for patients with ACH who are resistant to topical regimens. This recommendation is based on its proven efficacy, safety profile, and cost‐effectiveness compared to retinoids, methotrexate, cyclosporine, and biologics. Notably, it may serve as one of the first‐line systemic treatment options, especially for women of childbearing age.

Funding

The authors received no financial support for this study.

Consent

Written informed consent was obtained from the patients to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.