BASICS
- Acropustular eruption with a predilection for distal digits characterized by sterile pustules; early nail involvement; and a persistent, relapsing course
- Classified as a noninfectious neutrophilic dermatosis and variant of pustular psoriasis
- Synonym(s): acrodermatitis continua of Hallopeau; acrodermatitis perstans; dermatitis repens; pustular acrodermatitis
DESCRIPTION
- Acute-phase morphology
- Around and under the nail(s) are multiple, sterile, erythematous-based, painful pustules that coalesce to form polycyclic "lakes of pus,"Ł which subsequently rupture and crust.
- Chronic sequelae occur secondary to recurrent eruptions.
- Nail changes: paronychia, onychodystrophy, onycholysis, onychomadesis, and anonychia
- Scaling of the nail bed and periungual skin
- Sclerosis or atrophy of soft tissue adjacent and deep to nail bed
- Osteolysis of underlying bone, particularly distal phalanges
- Distribution
- Usually affects one to two digits, most frequently the first digits of the hands but may involve all fingers and toes
- Most often distal but may rarely spread proximally to involve feet, ankles, hands, and forearms
- Predilection for dorsal surfaces of hands and feet with sparing of central palmar and plantar regions
- Isolated proximal psoriatic plaques are rare.
EPIDEMIOLOGY
- Exceedingly rare: Only case studies and series are available.
- Female predominance
- Predominantly in adults but also seen in children: observed in 4.7% cases of infantile psoriasis in one series
ETIOLOGY AND PATHOPHYSIOLOGY
- Immune dysregulation: Acute-phase reactants such as IL-1 and IL-36 likely play a role in pathogenesis (1,2).
- In some instances, digital trauma or infection may be an inciting event.
Genetics
- Reported associations with mutations in the IL36RN gene, which codes for the IL36 receptor antagonist, and is a cause of familial generalized pustular psoriasis (2,3).
- No observed relationship with plaque psoriasis-associated alleles HLA-B13, B17, or BW37
RISK FACTORS
- History of psoriasis, particularly pustular variant
- Digital trauma
- Local infection
- Smoking may contribute to exacerbations.
COMMONLY ASSOCIATED CONDITIONS
- Palmoplantar pustular psoriasis (PPP)
- Generalized pustular psoriasis (GPP) (4)
- Psoriatic arthritis (5,6)
DIAGNOSIS
- Defined by clinical evolution and histopathologic features
- Frequently missed, often a diagnosis of exclusion
HISTORY
- Onset, including any triggering event
- Duration of eruption, previous episodes
- Local trauma or infection
- Impairment in manual dexterity or ambulation
- Localized symptoms: pain, pruritus, arthritis
- Systemic symptoms: fever, malaise, weight loss
- History of other immune disorder such as psoriasis, arthritis, or celiac disease
- Smoking history
PHYSICAL EXAM
- Examine all skin surfaces, nails, scalp, and mucous membranes.
- Examine and palpate joints, evaluating for swelling, erythema, or effusion.
- Palpate axillary, epitrochlear, and inguinal lymph nodes to assess for lymphadenopathy.
- Observe and evaluate gait and manual dexterity.
- Measure vital signs.
DIFFERENTIAL DIAGNOSIS
- Bacterial infection, especially staphylococcal
- Herpetic whitlow
- Cutaneous candidiasis
- Allergic contact dermatitis
- Dyshidrotic eczema
- Parakeratosis pustulosa (in children)
- Pemphigus vulgaris
- Squamous cell carcinoma, particularly in advanced disease
DIAGNOSTIC TESTS & INTERPRETATION
- Cultures are sterile, unless secondary infection is present.
- There are no characteristic serologic findings; however, acute systemic inflammation during flares may result in
- Increased neutrophil count
- Increased C-reactive protein
Initial Tests (lab, imaging)
- The following should be performed on fluid obtained from pustules:
- Gram stain smear
- Potassium hydroxide preparation
- In vitro culture
- X-rays of hands and feet may show acro-osteolysis, especially in long-standing disease. Ankle osteolysis may also be observed, and is usually unilateral.
Follow-Up Tests & Special Considerations
Additional laboratory tests may be necessary to monitor for side effects of treatment. á
Diagnostic Procedures/Other
Full-thickness cutaneous punch biopsy of an active pustule may establish diagnosis and should be performed (7,8). á
Test Interpretation
- Nail bed epithelium and adjacent epidermis
- Compact hyperkeratosis with parakeratosis with or without neutrophils
- Focal, subcorneal neutrophilic aggregates
- Spongiform pustules of Kogoj (leukocyte aggregates between epidermal cells, associated with spongiosis)
- Psoriasiform epidermal hyperplasia
- Hemorrhagic foci displaying erythrocytes and hemosiderin
- Dermis
- Superficial perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, and neutrophils
- Tortuous, dilated vessels displaying erythrocyte extravasation
- Edema of papillary dermis
TREATMENT
- Due to the rarity of this disease, only expert opinion and case reports are available to guide treatment recommendations.
- Notoriously refractory to treatment, including topical and systemic agents used successfully in psoriasis
- The agents listed below may be more effective when used in combination than as monotherapy.
- Repeated courses or prolonged treatment are often necessary.
GENERAL MEASURES
If cultures show secondary infection, treat with appropriate antibiotics. á
MEDICATION
- Topicals
- Topical agents generally have favorable side effect profiles but may be ineffective, especially as monotherapy. Application under occlusion enhances absorption:
- Vitamin D3 analogs, such as calcipotriol: alone or combined with topical tacrolimus, betamethasone dipropionate, or oral acitretin (8)
- Topical corticosteroids, with or without occlusion
- May be combined with an oral antibiotic such as a tetracycline (8)
- 5-Fluorouracil (8)
- Tacrolimus ointment, with or without occlusion (8)
- Anthralin (7)
- Systemics
- Systemic medications are generally more effective than topicals, although may be more expensive and carry increased risk of adverse effects.
- Tumor necrosis factor-╬▒ (TNF-╬▒) inhibitors
- Adalimumab has shown greatest effectiveness at 40 mg every 1 to 2 weeks (7,8,9,10); may also be safe and effective for pediatric patients (11)
- Etanercept 20 to 50 mg twice per week (8)
- Infliximab 5 mg/kg IV at 0, 2, and 6 weeks, then at 8-week intervals (8)
- Ustekinumab (9)
- Sometimes combined with oral acitretin, methotrexate, cyclosporine, or prednisone
- Cyclosporine (4,8)
- Methotrexate (6): alone or in combination with propylthiouracil
- Anakinra: alone or in combination with acitretin (1)
- Acitretin: possible synergistic effect with topical calcipotriol (8)
- Antibiotics
- Sulfones, namely dapsone
- Tetracyclines
- Colchicine
ADDITIONAL THERAPIES
- Phototherapy and photochemotherapy have been successful as monotherapies or in conjunction with medications.
- Targeted narrow band ultraviolet B phototherapy
- As monotherapy or in conjunction with systemic medications (8)
- Used successfully with thalidomide to treat a pediatric patient (12)
- Psoralen ultraviolet A
- With selective hand bath psoralen (8)
- Low-level polarized polychromatic noncoherent light (LPPL) plus 0.1% methylprednisolone aceponate cream
- Used successfully in a pregnant patient (13)
ISSUES FOR REFERRAL
If there is suspicion of psoriatic arthritis, refer to a rheumatologist. á
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Long-term management by a dermatologist á
PROGNOSIS
- Generally persistent, chronically relapsing course
- May lead to severe disability or complications warranting hospitalization
COMPLICATIONS
- Association with or progression to PPP or GPP
- Psoriatic arthritis (possible association)
- Pain and resultant loss of manual dexterity may have significant psychosocial impact.
- Fever and systemic inflammatory response syndrome
- Treatment-related complications, depending on agent used
REFERENCES
11 Lutz áV, Lipsker áD. Acitretin- and tumor necrosis factor inhibitor-resistant acrodermatitis continua of Hallopeau responsive to the interleukin 1 receptor antagonist anakinra. Arch Dermatol. 2012;148(3):297-299.22 Sugiura áK. The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants. J Dermatol Sci. 2014;74(3):187-192.33 Abbas áO, Itani áS, Ghosn áS, et al. Acrodermatitis continua of Hallopeau is a clinical phenotype of DITRA: evidence that it is a variant of pustular psoriasis. Dermatology. 2013;226(1):28-31.44 Ranugha áPS, Kumari áR, Thappa áDM. Acrodermatitis continua of Hallopeau evolving into generalised pustular psoriasis. Indian J Dermatol. 2013;58(2):161.55 Jo áSJ, Park áJY, Yoon áHS, et al. Case of acrodermatitis continua accompanied by psoriatic arthritis. J Dermatol. 2006;33(11):787-791.66 Okuno áH, Ogura áK, Okuyama áR, et al. Two cases of acrodermatitis continua of Hallopeau associated with generalized arthritis. Acta Dermatovenerol Croat. 2013;21(4):265-267.77 Razera áF, Olm áGS, Bonamigo áRR. Neutrophilic dermatoses: part II. An Bras Dermatol. 2011;86(2):195-211.88 Sehgal áVN, Verma áP, Sharma áS, et al. Acrodermatitis continua of Hallopeau: evolution of treatment options. Int J Dermatol. 2011;50(10):1195-1211.99 Di Costanzo áL, Napolitano áM, Patruno áC, et al. Acrodermatitis continua of Hallopeau (ACH): two cases successfully treated with adalimumab. J Dermatolog Treat. 2014;25(6):489-494.1010 Sopkovich áJA, Anetakis Poulos áG, Wong áHK. Acrodermatitis continua of Hallopeau successfully treated with adalimumab. J Clin Aesthet Dermatol. 2012;5(2):60-62.1111 Dini áV, Barbanera áS, Romanelli áM. Efficacy of adalimumab for the treatment of refractory paediatric acrodermatitis continua of hallopeau. Acta Derm Venereol. 2013;93(5):588-589.1212 Kiszewski áAE, De Villa áD, Scheibel áI, et al. An infant with acrodermatitis continua of Hallopeau: successful treatment with thalidomide and UVB therapy. Pediatr Dermatol. 2009;26(1):105-106.1313 Choi áM, Na áSY, Cho áS, et al. Low level light could work on skin inflammatory disease: a case report on refractory acrodermatitis continua. J Korean Med Sci. 2011;26(3):454-456.
CODES
ICD10
L40.2 Acrodermatitis continua á
ICD9
696.1 Other psoriasis á
SNOMED
- Acrodermatitis continua (disorder)
- Acrodermatitis continua of Hallopeau
- Localized acrodermatitis continua of Hallopeau (disorder)
CLINICAL PEARLS
- Rare variant of pustular psoriasis that preferentially affects the fingers and toes, often leading to significant pain and loss of function
- Classically refractory to treatment, although case reports show that a variety of agents may have limited efficacy. Adalimumab may be the most promising option.