Certolizumab Pegol: A New Therapeutic Approach for Acrodermatitis Continua of Hallopeau

Abstract

Introduction

Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic, and recurrent form of pustular psoriasis (PP) localized to one or more digits. Due to the rarity of ACH, no clear treatment guidelines are currently available, making the therapeutic approach more complex.

Case Presentation

We report the first case of a young woman with ACH who was successfully treated with certolizumab pegol (CZP).

Discussion/Conclusion

PP and ACH are difficult to treat, and biologics may be an option more manageable than cyclosporine. CZP is the safest biologic therapy during pregnancy, so there is low risk in prescribing it in women with childbearing potential. However, continuing biological therapy during pregnancy always involves an assessment of the clinical benefits, which must outweigh the risks.

Established Facts

• Acrodermatitis continua of Hallopeau (ACH), if not adequately treated, evolves over time leading progressively to osteolysis of the distal phalanges.

• Due to the rarity of ACH, no clear treatment guidelines are currently available.

• Topical and systemic therapies with antipsoriatic drugs (methotrexate, corticosteroids, cyclosporine, tetracyclines, retinoids, colchicine, and dapsone) have shown ambiguous and often time-limited results.

Novel Insights

• Certolizumab pegol was effective in disease remission and allowed for nail regrowth.

• Certolizumab pegol may be the safest therapeutic option in a young woman of childbearing age affected by pustular psoriasis.

Introduction/Literature Review

Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic, and recurrent form of pustular psoriasis (PP) localized to one or more digits [1]. It is characterized by the eruption of sterile pustules and erythema on the extremities, more frequently on the hands than the feet, always involving the nails [2]. If not adequately treated, ACH evolves over time leading progressively to onychodystrophy, anonychia, and osteitis, up to osteolysis of the distal phalanges [2]. The impact on quality of life can be devastating, which is why timely and effective treatment is necessary.

Due to the rarity of ACH, no clear treatment guidelines are currently available, making the therapeutic approach more complex [3]. We report a case of a young woman with ACH who was successfully treated with certolizumab pegol (CZP).

Case Report/Case Presentation

A 29-year-old woman, with no previous medical history and no family history for psoriasis or psoriatic arthritis, complained of symmetrically located subungual pustules and erythema on the extremities of both phalanges of her third finger and both first toes for about 3 months. She denied trauma or previous localized infectious episodes. On physical examination (Fig. 1a, b), the nails appeared severely dystrophic, with destruction of the nail plate in the anterior portion and painful on palpation. No pustules were visible at the time of the first examination. Cell blood count, blood chemistry, and C-reactive protein were in the normal range. Since the clinical and anamnestic features were extremely suggestive for ACH, we decided not to perform a nail biopsy, according to the patient's preference. After oral administration of cyclosporine 200 mg/day, the patient reported a slight initial progressive growth of the nail plate at 4 weeks (Fig. 1c–f) and at 8 weeks, but pustule formation persisted on the extremities of the fingers and were clinically evident (Fig. 1g, h). Moreover, the patient complained of gastrointestinal symptoms related to the intake of the drug. We therefore decided to switch to injection therapy with the TNF-α inhibitor CZP at a dosage of 400 mg subcutaneously at weeks 0, 2, and 4 followed by 200 mg every 2 weeks, after all necessary exams were in the normal range (blood test, Mantoux test, chest X-ray, and abdomen echography). After 8 weeks, no new pustules formed. The nail plate of the fingers grew with good adhesion to the nail bed (Fig. 1j), resulting in patient satisfaction and a significant improvement in quality of life. The toenails improved as well, but maintained dystrophic features, probably due to the daily work-related traumatization of the feet (Fig. 1i). After 10 months of therapy, the patient showed continuous improvement of the fingernails with almost complete adhesion to the nail bed (Fig. 1l). The toenails improved moderately, maintaining the dystrophic appearance (Fig. 1k).

Fig. 1.

a, b The left and right first toe and the left and right third finger before treatment. The nails appeared severely dystrophic, with destruction of the nail plate in the anterior portion. No pustule visible. In the distal lateral nail quadrant of the second finger of the right hand, there is an oil spot. Total NAPSI: 34/160; nails after 4 weeks of cyclosporine 200 mg/day (c–f). Partial proximal nail regrowth; nails after 8 weeks of cyclosporine 200 mg/day (g, h). Further regrowth of extremely weak, brittle, and raised nails. Evidence of pustules in the nail bed; nails after 8 weeks of certolizumab pegol at a dosage of 400 mg at weeks 0, 2, and 4 followed by 200 mg every 2 weeks (i, j). The nail plate of the fingers grew with excellent adhesion to the nail bed. The toenails improved, maintaining dystrophic features. No pustule visible. Total NAPSI after 8 weeks: 20/160, with a reduction of 40%. k, l Nails after 10 months of therapy with certolizumab pegol 200 mg every 2 weeks. The nail plate of the fingers shows further improvement, lengthening of the portion adhering to the nail bed. Only a small distal area is not adherent to the nail bed. The toenails improved moderately, maintaining the dystrophic appearance, probably related to repeated daily work-related traumas. No visible pustules and no symptoms. Total NAPSI after 10 months: 16/160, with a reduction of about 53%. NAPSI, Nail Psoriasis Severity Index.

Discussion/Conclusion

Treatment of ACH is challenging since there are no well-defined indications, and the needs and comorbidities of the single patient must be considered. Topical and systemic therapies with antipsoriatic drugs (methotrexate, corticosteroids, cyclosporine, tetracyclines, retinoids, colchicine, and dapsone) have shown ambiguous and often time-limited results [1]. There are numerous case reports in the literature evaluating the efficacy of TNF-α inhibitors (infliximab, etanercept, and adalimumab), IL-12/23 inhibitors (ustekinumab), and IL-17 inhibitors (secukinumab and ixekizumab) [4]. Biological drugs were used after the failure of conventional drugs and often in combination with other systemic therapies. Adalimumab was one of the most successful reported monotherapies with 6 cases treated [4].

In our case, the patient is a young woman of childbearing age, so the administration of a biological drug should have been discontinued in the event of pregnancy, exposing the patient to the risk of disease progression. We then decided to administer CZP, a PEGylated, Fc-free TNF-α inhibitor that appears not to cross the placenta and is, actually, a low-risk treatment in pregnancy [5, 6]. Other anti-TNF-α may be administered during pregnancy, such as adalimumab or etanercept, but the use of Fc-containing biologics during the third trimester is not recommended [7].

In a study by Mizutani et al. [5], a pregnant woman with generalized pustular psoriasis was treated with CZP, achieving a rapid clinical response after the second administration. In our case, the patient reported the disappearance of acral pustules after a single injection, underlining the rapid onset of action of CZP. In the literature, among the biologics used in monotherapy, secukinumab was the fastest (2 cases, from one-time treatment to 6 weeks), while the others showed more variability, such as adalimumab (6 cases, 1–10 months), etanercept (3 cases, 2–9 months), ixekizumab (1 case, 3 months), ustekinumab (2 cases, 7–21 months), and infliximab (3 cases, 18–40 months) [4].

To the best of our knowledge, this is the first and the only case in the literature in which CZP is used successfully for the treatment of ACH. Further studies with a larger sample size are needed to confirm the long-term efficacy of this therapy and to create consensus guidelines. In conclusion, PP and ACH are difficult to treat, and biologics may be an option more manageable than cyclosporine. CZP is the safest biologic therapy during pregnancy, so there is low risk in prescribing it in women with childbearing potential. However, continuing biological therapy during pregnancy always involves an assessment of the clinical benefits, which must outweigh the risks. Finally, PP and ACH are pathogenically different from psoriasis because the main signal implicated seems to be IL-36 [8], so probably in the near future, when anti-IL-36 will be available, better results could be achieved.

Statement of Ethics

The patient has given written informed consent to publish this case (including publication of images). Ethical approval was not required for this study in accordance with the national guidelines.

Conflict of Interest Statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Funding Sources

This study was not funded.

Author Contributions

G. Rizzetto and A.M. Offidani contributed to conception and design of the study; F. Diotallevi contributed to analysis and interpretation of data; G. Radi contributed to acquisition of data; E. Molinelli and A.M. Offidani contributed to approval of the version of the manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.