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Acrodermatitis Continua

BASICS

- 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.

- The following should be performed on fluid obtained from pustules: - Gram stain smear - Potassium hydroxide preparation - In vitro culture

- 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

- 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

  • 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 morphologyAround 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 anonychiaScaling of the nail bed and periungual skinSclerosis or atrophy of soft tissue adjacent and deep to nail bedOsteolysis of underlying bone, particularly distal phalanges
  • DistributionUsually affects one to two digits, most frequently the first digits of the hands but may involve all fingers and toesMost often distal but may rarely spread proximally to involve feet, ankles, hands, and forearmsPredilection for dorsal surfaces of hands and feet with sparing of central palmar and plantar regionsIsolated 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 inIncreased neutrophil countIncreased C-reactive protein

Initial Tests (lab, imaging)

  • The following should be performed on fluid obtained from pustules:Gram stain smearPotassium hydroxide preparationIn 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 epidermisCompact hyperkeratosis with parakeratosis with or without neutrophilsFocal, subcorneal neutrophilic aggregatesSpongiform pustules of Kogoj (leukocyte aggregates between epidermal cells, associated with spongiosis)Psoriasiform epidermal hyperplasiaHemorrhagic foci displaying erythrocytes and hemosiderin
  • DermisSuperficial perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, and neutrophilsTortuous, dilated vessels displaying erythrocyte extravasationEdema 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

  • TopicalsTopical 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 occlusionMay be combined with an oral antibiotic such as a tetracycline (8)5-Fluorouracil (8)Tacrolimus ointment, with or without occlusion (8)Anthralin (7)
  • SystemicsSystemic medications are generally more effective than topicals, although may be more expensive and carry increased risk of adverse effects.Tumor necrosis factor-╬▒ (TNF-╬▒) inhibitorsAdalimumab 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 prednisoneCyclosporine (4,8)Methotrexate (6): alone or in combination with propylthiouracilAnakinra: alone or in combination with acitretin (1)Acitretin: possible synergistic effect with topical calcipotriol (8)AntibioticsSulfones, namely dapsoneTetracyclinesColchicine

ADDITIONAL THERAPIES

  • Phototherapy and photochemotherapy have been successful as monotherapies or in conjunction with medications.
  • Targeted narrow band ultraviolet B phototherapyAs monotherapy or in conjunction with systemic medications (8)Used successfully with thalidomide to treat a pediatric patient (12)
  • Psoralen ultraviolet AWith selective hand bath psoralen (8)
  • Low-level polarized polychromatic noncoherent light (LPPL) plus 0.1% methylprednisolone aceponate creamUsed 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.