Are You Confident of the Diagnosis?

Acrodermatitis continua of Hallopeau (ACH), a rare and chronic eruption of sterile pustules associated with hyperkeratosis and skin atrophy on the distal fingers and toes, is considered by many to be a localized variant of pustular psoriasis. The name is attributed to French dermatologist Francois Hallopeau, who described a relapsing bullous and pustular eruption of the hands and feet in 1890.

Correlating the gross findings with the clinical history makes the diagnosis of ACH. The disorder is characterized by recurrent, acute, self-limited episodes of painful, inflammatory peri- and subungual pustules often limited to a single digit, although frequently multiple digits are involved. Uncommonly, ACH presents in a more generalized form with nonacral skin also involved, but such a presentation is typically classified as pustular psoriasis.

  • Characteristic findings on physical examination

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On physical examination, ACH most often presents at the nail folds of one or two fingers, less frequently on the toes, with small, erythematous pustules that frequently coalesce to form diminutive lakes of pus (Figure 1). As individual lesions progress, the affected areas often become hyperkeratotic and scaly as new pustules continue to develop underneath the fissured surface. Over time the skin in these areas may become severely atrophic with shiny erythema. Most often patients present with involvement of the nail and dorsal aspect of a single digit, but any number may be involved, as can the palms and soles. Over time, ACH may also extend proximally to involve and even cover the dorsal portions of the hands, forearms, ankles, and feet (Figure 2). Relapsing episodes of pustular inflammation are common and often quite painful, but some patients are largely asymptomatic.

Figure 1.

Palmar involvement with erythematous hyperkeratosis, pustules, and lakes of pus.

Figure 2.

A focal area of acral pustulation after proximal extension.

Nail involvement is central to the diagnosis of acrodermatitis continua of Hallopeau, with a majority of patients reporting or displaying some degree of nail pathology. Pustulation, more commonly within the nail bed but also within the nail matrix, often leads to more severe sequelae such as considerable pain, onychodystrophy, onycholysis, or onychomadesis. With frequent recurrences and long duration of disease, there may be complete destruction of the nail matrix and permanent nail loss, or anonychia. Nail involvement is not required for diagnosis, however.

With more severe disease, over time the local inflammation may induce sclerosis of underlying soft tissue, muscular atrophy, arthropathy of interphalangeal joints, and osteolysis with resorption of the distal phalanx (Figure 3). This process may be quite disabling, and patients may complain of pain and limited motion. Rarely, ACH is associated with oral involvement in the form of annulus migrans, or geographic tongue.

Figure 3.

Anonychia, pustulation, hyperkeratosis, and soft tissue sclerosis in a patient with chronic disease.

  • Expected results of diagnostic studies

Laboratory studies should be directed at ruling out other disorders in the differential diagnosis, given that systemic abnormalities are typically absent and there are no pathognomonic or characteristic laboratory findings. Cultures may be helpful in ruling out secondary infections of bacteria, viruses, or fungi, but results are usually negative as the pustules of ACH stem from a sterile inflammatory process. Bacterial cultures may grow other normal saprophytic flora of the skin, but these are not typically implicated in the pathogenesis of this disease. Viral cultures, direct fluorescent antibody assay, or polymerase chain reaction (PCR) may be helpful to rule out viral paronychias.

A skin biopsy is rarely necessary, as the clinical history and cutaneous findings allow the diagnosis to be made with confidence. In equivocal cases where a peri- or subungual biopsy is deemed necessary, the histologic picture is similar to that of pustular psoriasis, the most closely related disorder in the differential diagnosis (Figure 4).

Figure 4.

Spongiotic epidermal hyperplasia with neutrophils forming central pustule. (H&E)

In the epidermis, mounds of compact parakeratosis with neutrophils staggered throughout the stratum corneum are seen, along with mild, psoriasiform epidermal hyperplasia, hypogranulosis, elongated rete ridges, and focal, subcorneal aggregates of additional neutrophils forming spongiform pustules. These pustules, known as “spongiform pustules of Kogoj”, differ from those seen in pustular psoriasis in that there may be little epidermal necrosis in early stages of ACH. However, necrosis may be evident in later stages.

In the superficial dermis, moderately dilated vessels with a surrounding lymphohistiocytic infiltrate and few extravasated erythrocytes are often seen. In the chronic phase, along with epidermal thinning, the dermal vessels are more dilated and tortuous, and the edema of the often atrophic papillary dermis is denser as is the superficial infiltrate of lymphocytes, histiocytes, and neutrophils. Foci of hemorrhage with extravasated erythrocytes and hemosiderin may be seen at any stage, particularly in biopsies of the nail bed.

In less advanced disease, there is little value in imaging studies. But imaging studies may be warranted in advanced cases, with plain radiographs showing atrophy and osteolysis of the distal phalanx, arthropathy of the interphalangeal joints, and serving to help establish the aggressiveness and severity of disease. X-rays may also show sclerosis of underlying soft tissue in severely affected joints.

  • Diagnosis confirmation

ACH must be differentiated from pustular psoriasis and acute, infectious paronychia. The differential is as follows:

Pustular psoriasis. As compared to psoriasis, with ACH the association of local trauma as the initial triggering factor is more established, the lesions are painful, and involvement is typically limited to distal fingers and toes with palmoplantar sparing. In addition, with ACH the characteristic nail involvement occurs earlier than with psoriasis, and thus loss of the nail plate is also more frequent.

Unlike psoriasis, there is often no family history of related disease in patients with ACH, there is no genetic association to specific HLA types, underlying bone may be involved leading to mutilation, and the response to commonly used medications for psoriasis is poor. On histology, Kogoj spongiform pustules, a hallmark of pustular psoriasis, lead many to consider ACH a variant of the disease, while others believe ACH may transition over time into generalized pustular psoriasis, especially in the elderly.

Palmoplantar pustulosis (PPP). ACH can be distinguished from PPP, a localized form of pustular psoriasis, and pustular dyshidrotic eczema by the localization on the distal extremities, the propensity for the pustules to coalesce and become confluent, and the presence of atrophy and nail loss.

Acute contact dermatitis. As compared to ACH, lesions of acute contact dermatitis are more commonly vesicular rather than pustular, palmoplantar involvement is more common, margins are typically less clearly defined, and disease is less persistent and more responsive to therapy.

Pustular dyshidrotic eczema. As with palmoplantar pustulosis, ACH can be distinguished from pustular dyshidrotic eczema by the more distal localization, the propensity for pustules to coalesce, and the presence of atrophy and nail loss.

Bacterial or viral paronychia. Early ACH and bacterial or viral paronychia may be easily confused owing to the relapsing course and chronic purulent discharge. A relapsing course is not typical of bacterial infections, but is typical of both ACH and viral infections, which can be differentiated by viral culture, direct fluorescent antibody assay, or PCR. Herpes simplex virus (HSV) is the most common viral paronychia, and should be suspected if pain is grossly out of proportion to cutaneous findings.

Onychomycosis. Onychomycosis rarely presents with pustules, but may also have accompanying peri- or subungual inflammation. In contrast to ACH, onychomycosis more commonly affects the toes rather than fingers. A positive fungal culture is diagnostic for onychomycosis, but does not rule out ACH.

Parakeratosis pustulosa. A similar disease occurring only in children, this psoriasiform disorder, characterized by mild subungual hyperkeratosis, fingertip desquamation, and onycholysis, is usually limited to one finger and resolves spontaneously at puberty.

ACH can occur at any age, including children and the elderly, but middle-aged women are the most commonly affected. This rare condition usually occurs after minor trauma or infection of a single digit, but such an event is not always reported or identified. Patients with ACH rarely have any additional features of psoriasis. A positive family history of related disorders is uncommon, and no familial forms or associated genes have been identified.

What is the Cause of the Disease?

  • Etiology

The etiology of acrodermatitis continua of Hallopeau is largely unknown, with some clinicians believing the comparable histopathologic picture classifies the disorder as a subtype of pustular psoriasis, while others consider it a separate entity given the distinct clinical findings and course.

Up to 80% of patients have involvement of only one digit, usually the first finger, and proximal spread may occur slowly, progressing even after many years. ACH typically has a chronic, relapsing course and may evolve into generalized pustular psoriasis over time. The chronic phase is characterized by nail bed hemorrhage, atrophy, and periungual desquamation. Spontaneous resolution is rare, and the disease may be aggressive with soft-tissue sclerosis and muscular atrophy, bone involvement with resorptive osteolysis, or loss of the distal parts of fingers or toes.

ACH is very difficult to treat and often recurs even with successful treatment.

  • Pathophysiology

The pathogenesis of ACH is unclear, but it is believed that following local trauma or infection, an immune system dysregulation and amplification occurs, with neutrophils releasing proteases, cytokines, and chemokines that in turn recruit macrophages and T lymphocytes. The macrophages and T cells in turn release their own chemokines and mediators, perpetuating the cycle. A dense infiltrate of neutrophils and other inflammatory cells thus creates the characteristic pustules. A central role of T lymphocytes and cytokines such as tumor necrosis factor-α (TNF-α) and possibly interleukin (IL)-1, is supported by the reports of success with cyclosporine, TNF-α inhibiting biologics, and IL-1 pathway antagonist, respectively.

Systemic Implications and Complications

Systemic complications are typically absent, but clinicians must be aware of the spectrum of local disease that may develop. With recurrence of pustular lesions, onycholysis, onychodystrophy, and anonychia may occur. Moreover, with aggressive disease there may be sclerosis of local soft tissue, and bony resorptive osteolysis leading to loss of the distal portions of fingers or toes.

Over time, ACH may evolve into generalized pustular psoriasis, at which point the treatment should shift to the algorithm for that disease.

Treatment Options

Treatment options are summarized in Table I.

TOPICAL Phototherapy (Narrowband UVB or PUVA*) Not typically indicated
Potent or superpotent topical corticosteroids Intralesional corticosteroids
Oral retinoids

*PUVA, psoralen plus ultraviolet A, UVB, ultraviolet B

Optimal Therapeutic Approach for this Disease

ACH is not considered a systemic disease; thus, local, topical treatments are first line therapy. However, given how recalcitrant the disease classically is to conventional therapy, systemic agents are often necessary and employed. The regimens are similar to those for psoriasis and hand eczema. There are numerous topical agents that may be beneficial.

To lessen the inflammation and pustulation, topical corticosteroids, either potent (betamethasone 0.05%) or ultrapotent (clobetasol 0.05%), may help. Additional topical agents shown to be beneficial include tacrolimus (0.1% ointment), calcipotriol (0.005% cream or ointment), or topical 5-fluorouracil. Success has been reported with a variety of combinations of the above topical therapeutics, with or without adjunctive use of an oral retinoid. All topicals may be used with or without occlusion, and caution is advised with already atrophic skin. Given the propensity for atrophy in ACH, consider a pulsed regimen of topical corticosteroids to minimize the atrophic effects of the drug. Intralesional corticosteroids (5 mg/cc) may also be helpful.

As a poor response is often seen to topical options, systemic agents are routinely utilized. The limited literature of ACH treatment options is robust with successful use of oral retinoids such as acitretin (0.3 mg/kg/day) or etretinate, depending on regional availability.

Success has also been seen with immunomodulators, with numerous reports showing a successful response to cyclosporine, methotrexate(7.5-20 mg weekly in either oral or intramuscular formulations), and thalidomide (100-300 mg QD) and ultraviolet (UV) B. For recalcitrant patients, anecdotal reports also recommend dapsone and nimesulide to prevent relapses. Nimesulide is not available in the United States, however, as the drug has not been approved by the FDA over concerns of dose-limiting hepatotoxicity. These reports are limited, and further studies are needed.

More aggressive cases with bony involvement, muscle and soft-tissue sclerosis and atrophy, or significant resorptive osteolysis and mutilation may require systemic steroids such as prednisone (start at 1 mg/kg/day).

More recently, many have reported significant therapeutic benefit with the anti-TNF-α biologic medications, notably infliximab (IV infusion induction 5 mg/kg at 0, 2, and 6 weeks, then 5 mg/kg every 6-8 weeks, increase to 10 mg/kg if diminishing response, consider discontinuing by week 14 if no response), adalimumab (40 mg subcutaneously every 2 weeks), and in particular etanercept (50 mg subcutaneously weekly). The latter two were reported with and without adjunctive acitretin. The authors tend to always combine biologic medications with methotrexate (7.5-20 mg weekly) so as to inhibit the development of immunogenicity and subsequent loss of response. Ustekinumab, an anti-IL-12/23 agent approved for moderate to severe psoriasis, either as monotherapy or combined with a systemic retinoid, has also been used with inconsistent results. Anakinra, an IL-1 receptor antagonist, was used successfully in an ACH patient who failed a combination of a systemic retinoid and a TNF-α inhibitor, as well as systemic retinoid combined with ustekinumab. Due to the small number of cases reported, the efficacy of ustekinumab and anakinra remains to be determined.

Phototherapy with psoralen plus UVA (PUVA) or targeted narrow-band UVB may help suppress new eruptions and assist with long-term maintenance.

Inquire as to functional disability of the patient, as milder cases of more cosmetic concern can be managed less aggressively.

Patient Management

Treatment of ACH is notoriously difficult and the results are frequently disappointing and unsatisfactory. The clinician must take care to consider all therapeutic options as numerous agents and modalities are often required to manage this condition. Combination therapy may yield synergistic results that exceed the effect of either agent as monotherapy.

Alternative strategies such as hand protection with cotton gloves may also be of benefit, particularly with more brittle nails.

Care should be taken with pregnant patients or females of child-bearing age, as some of the typical therapeutic agents are contraindicated during gestation.

Explain to the patient that ACH is a chronic disease that not only frequently relapses but also has the potential to cause significant local morbidity or evolve into generalized pustular psoriasis. It is important to manage expectations of the lack of a cure or ‘magic bullet’ to maintain an effective clinical rapport with the patient.

Patients need to be seen only periodically (every 4-6 months), for mild disease requiring only topical therapy. Patients with more severe disease requiring systemic therapy should be seen more frequently (every 1-3 months), in accordance with the appropriate monitoring for that drug or modality.

Unusual Clinical Scenarios to Consider in Patient Management

Aggressive disease with overt mutilation and loss of the distal portion of the digit may occur, and preceding treatment should be aggressive to prevent such long-term morbidity.

What is the Evidence?

Brill, TJ, Elshorst-Schmidt, T, Valesky, EM, Kaufmann, R, Thaçi, D. “Successful treatment of acrodermatitis continua of Hallopeau with sequential combination of calcipotriol and tacrolimus ointments”. Dermatology. vol. 211. 2005. pp. 351-5. (An excellent overview of this disorder, a review of treatment options, and demonstration of the successful use of topical calcipotriol and tacrolimus.).

Gluckman, SJ, Heymann, W. “Diagnosis: acrodermatitis continua of Hallopeau”. Clin Infect Dis. vol. 32. 2001. pp. 431(A thorough review of the clinical features and background of ACH. The highlight of this paper is the excellent gross images of the disease that serve as prime examples.)

Nikkels, AF, Nikkels-Tassoudji, N, Piérard, GE. “Breaking the relentless course of Hallopeau's acrodermatitis by dapsone”. Eur J Dermatol. vol. 9. 1999. pp. 126-8. (This paper focuses on the successful therapeutic use of dapsone but in the process gives an outstanding review of therapeutic options. There is also a sound discussion of pathophysiologic theories for the disease.)

Yerushalmi, J, Grunwald, MH, Hallel-Halevy, D, Avinoach, I, Halevy, S. “Chronic pustular eruption of the thumbs. Diagnosis: acrodermatitis continua of Hallopeau (ACH)”. Arch Dermatol. vol. 136. 2000. pp. 925-930. (While brief, this paper represents an outstanding overview of the condition.)

Piraccini, BM, Tosti, A, Iorizzo, M, Misciali, C. “Pustular psoriasis of the nails: treatment and long term follow-up of 46 patients”. Br J Dermatol. vol. 144. 2001. pp. 1000-5. (A thorough review of the disorder, giving insight and recommendations particularly regarding diagnosis and therapy. This paper centers around the authors' experience with 46 patients, one of the largest groups published for this disease.)

Rosenberg, BE, Strober, BE. “Acrodermatitis continua”. Dermatol Online J. vol. 10. 2004. pp. 9(A case report and excellent overview of the condition.)

Razera, F, Olm, GS, Bonamigo, RR. “Neutrophilic dermatoses: part II”. An Bras Dermatol. vol. 86. 2011. pp. 195-211. (This paper discusses neutrophilic dermatoses, and the section on ACH is an outstanding overview of the disease. This paper provides an extremely current and robust review of therapeutic options and discusses proposed pathophysiologic mechanisms in detail.)

Ryan, C, Collins, P, Kirby, B, Rogers, S. “Treatment of acrodermatitis continua of Hallopeau with adalimumab”. Br J Dermatol. vol. 160. 2009. pp. 203-5. (This paper highlights the use of adalimumab as a treatment option and supports the use of biologic, anti-TNF therapy. As this disease is so difficult to treat, all modalities must be considered.)

Bordignon, M, Zattra, E, Albertin, C, Belloni-Fortina, A. “Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy”. Photodermatol Photoimmunol Photomed. vol. 26. 2010. pp. 41-3. (Phototherapy may be beneficial in treatment, as demonstrated by this report. The discussion of therapy is also excellent, reiterating the need for broad thinking in treatment.)

Mahowald, ML, Parrish, RM. “Severe osteolytic arthritis mutilans in pustular psoriasis”. Arch Dermatol. vol. 118. 1982. pp. 434-7. (ACH may be quite aggressive, and this paper serves to highlight the severe sequelae that may occur.)

Di Costanzo, L, Napolitano, M, Patruno, C, Cantelli, M, Balato, N. ” Acrodermatitis continua of Hallopeau (ACH): two cases successfully treated with adalimumab”. J Dermatolog Treat.. vol. 25. 2014. pp. 489-94. (This paper provides an excellent literature review on all topical and systemic treatments that have been utilized in ACH treatment up to the end of 2014.)

Saunier, J, Debarbieux, S, Jullien, D, Garnier, L, Dalle, S, Thomas, L. ” Acrodermatitis continua of Hallopeau treated successfully with ustekinumab and acitretin after failure of tumor necrosis factor blockade and anakinra”. Dermatology. . vol. 230. 2015. pp. 97-100. (A case report describing a very recalcitrant case of ACH being successfully treated with ustekinumab and acitretin. Furthermore, this manuscript also provides an excellent review of the pathogenesis of ACH.)

Lutz, V, Lipsker, D. ” Acitretin- and tumor necrosis factor inhibitor-resistant acrodermatitis continua of Hallopeau responsive to the interleukin 1 receptor antagonist anakinra”. Arch Dermatol. . vol. 148. 2012. pp. 297-9. (A case report describing successful treatment of recalcitrant ACH with anakinra. It further explores the possible involvement of IL-1 in the pathogenesis of ACH.)