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Acrodermatitis Chronica Atrophicans
Introduction
Acrodermatitis chronica atrophicans (ACA) is a late and chronic manifestation of Lyme borreliosis. ACA predominantly involves the distal portions of extremities and is characterized by chronic cutaneous atrophy.[1] Unlike other skin manifestations of Lyme disease, including erythema migrans and borrelial lymphocytoma, ACA does not spontaneously resolve. If untreated, ACA may progress from bluish-red discoloration and inflammation to chronic atrophy and fibrosis, with the late-stage being more treatment-resistant. ACA was first described in Germany in 1883 by Buchwald, and cases were later reported in North America in 1895.[2] The diagnosis of ACA is based on clinical presentation, as well as serologic testing and histopathologic confirmation. Recognizing ACA is often challenging due to variable latency in disease onset following the primary borrelial infection and lack of symptoms leading to delay in seeking treatment.
Lyme borreliosis is the most common vector-borne disease in the northeastern United States. It is a multisystem disease caused by the spirochete Borrelia burgdorferi.[3][4][5] It is transmitted to humans via an Ixodes tick bite. There are 3 skin manifestations of Lyme borreliosis: erythema migrans (stage 1) with a characteristic “bull’s eye rash,” which, if untreated, can be followed by early disseminated infection, borrelial lymphocytoma (stage 2) along with neurologic and cardiac abnormalities, and late infection, especially arthritis in North America or ACA (stage 3) in Europe.[6][7][8][9] ACA is the most common late and chronic manifestation of Lyme borreliosis. Approximately 20% of patients with ACA have a history of spontaneously healed EM, usually on an extremity where the ACA lesion developed 6 months to 8 years later.[1]
Etiology
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Etiology
Borrelia is a member of the Spirochaetacea family. There are approximately 20 different genospecies, but only 5 pose a significant pathogenic risk to humans: B. afzelii, B. garinii, B. bavariensis, B. burgdorferi sensu stricto, and B. spielmanii.[10] ACA results predominantly from bacterial infection with B. afzelii. However, it can also be caused by European B. burgdorferi sensu stricto or B. garinii.
Epidemiology
ACA predominantly affects women who are 40-70 years of age. ACA is rare in the pediatric population, with few cases reported in children.[11] It is more commonly seen in Europe due to untreated infection with Borrelia afzelii and is rarely found in the United States. The overall prevalence of ACA in patients with Lyme disease in Europe is approximately 10%.
Pathophysiology
The pathogenesis of Lyme disease involves the Ixodes tick feeding on an infected animal reservoir. The Borrelia spirochetes replicate, and some penetrate out of the tick’s midgut and migrate to the salivary glands.[12] When the tick bites a human, it releases spirochetes into the dermis via saliva. This results in an innate immune response with neutrophil migration and macrophage activation, causing the release of pro-inflammatory cytokines. Increased blood flow to the capillaries leads to erythema migrans at the bite site approximately 1 to 2 weeks later.[13] If untreated, there is hematogenous spread and development of systemic symptoms. In ACA, a chronic T-cell mediated immune reaction against Borrelia with CD3+ and CD4+ cells in the dermal infiltrate.[14][15] Borrelia binds to extracellular matrix proteins, including glycosaminoglycan-binding protein, fibronectin-binding protein, and decorin proteoglycan.[16][17][18] They activate metalloproteases and cause degradation of the extracellular matrix. Borrelia also have a high affinity for collagen fibers, as demonstrated by electron microscopy.[19][20] Damage to connective tissues, with the destruction of collagen, leads to fibrosis and dermal atrophy.[21][22][23][24]
Histopathology
In the early inflammatory stage, biopsy specimens of active lesions show perivascular lymphocytic infiltrate with plasma cells in the dermis, telangiectatic endothelial-lined spaces, and mild atrophy of the epidermis. Histological examination of late lesions demonstrates an atrophic epidermis and interstitial lymphocytic infiltrate with plasma cells and occasional histiocytes or mast cells.[7][25]
History and Physical
Most patients may not recall a tick bite due to the delayed progression of ACA. Furthermore, diagnosis is quite challenging due to varying clinical manifestations. ACA is considered biphasic; it initially presents as bluish-red lesions overlying doughy and swollen skin. It later progresses to extensive skin atrophy with a prominence of underlying blood vessels and a shiny appearance or “cigarette paper skin.” Lesions are primarily located on the bilateral extensor surfaces of the limbs. Fibroid nodules may develop over bony prominences, especially in the ulnar or tibial regions.[26] In 15% of the patients with ACA, a localized increase of collagen leads to band-like induration with decreased movement of the joints.[27] Peripheral neuropathy can occur in approximately half of the patients, with associated numbness, tingling, or allodynia.[28] Enlargement of the limb with tenosynovitis and dactylitis is a rare occurrence.[29][30][31]
Evaluation
The diagnosis of ACA is based on clinical findings and supported by serologic tests (high level of specific Borrelia IgG antibodies).[32] Serology is positive for Borrelia IgG antibodies in most chronic Lyme disease patients. IgM antibodies against Borrelia are often false positives in the late stages and thus are not useful in diagnosing ACA.[33] A negative serologic test excludes ACA. When the clinical picture is uncertain, further diagnosis is made with a skin biopsy and histological examination. Detection of B. burgdorferi DNA by culture or PCR helps confirm the diagnosis.[5]
Treatment / Management
The standard management is based on the administration of 1 of the following antibiotics:
- Oral amoxicillin 500 to 1000 mg 3 times daily for 14 to 28 days
- Oral doxycycline 100 mg twice daily or 200 mg once daily for 14 to 28 days
- Intravenous ceftriaxone 2000 mg every 24 hours for 14 to 28 days
- Intravenous cefotaxime 2000 mg every 8 hours for 14 to 28 days
- Intravenous penicillin G 3 to 4 MU every 4 hours for 14 to 28 days[34][35]
Differential Diagnosis
The differential diagnosis of ACA depends on the clinical presentation and disease stage. Lesions on the lower extremities are often mistaken as vascular insufficiency (ie, chronic venous or arterial insufficiency, superficial thrombophlebitis), cold injury, livedo reticularis, localized scleroderma, erysipelas, lymphedema, related to chronic use of potent topical corticosteroids or aging. Nodules may be confused with rheumatoid disease, gout, or erythema nodosum.[5]
Prognosis
The clinical outcome is positive if the acute inflammatory stage is treated appropriately. The clinical outcome is difficult to predict for the chronic atrophic phase, as changes are only partially reversible. One study showed that third-generation cephalosporin therapy for 28 days resulted in partial dissolving to fade the skin lesion completely.[1][36] If the skin lesion is left untreated, it does not typically resolve spontaneously, and fibrosis and atrophy can occur. Moreover, antibiotic therapy may not reverse neurologic symptoms, such as polyneuropathy (ie, pain, paresthesia).
Complications
ACA skin lesions may lead to bacterial superinfections. ACA is also considered a risk factor for malignancies, including B-cell lymphoma, basal cell carcinoma, and squamous cell carcinoma.[37]
Deterrence and Patient Education
The diagnosis of ACA is often delayed as patients do not report significant symptoms or seek medical attention, and due to the natural history of the disease developing months to years after a tick bite. Cutaneous lesions in ACA are mostly present on the extremities but may be located in other areas, including the abdomen or face, necessitating serologic and histopathologic confirmation. Treatment should be implemented as early as possible to prevent irreversible skin damage. Lyme borreliosis can be primarily prevented by avoidance of tick bites. Individuals should use personal protective measures to keep them safe when walking in wooded areas. These include applying repellents, wearing long sleeves, tucking pant legs into socks or long boots, and wearing light-colored clothing to make ticks more readily visible.[38] When returning from the outdoors, changing clothing and examining the body for ticks is crucial. If a tick is found, individuals should use fine-tipped tweezers to grasp the organism as close to the surface of their skin as possible, pull upwards to remove the tick, dispose of it appropriately, and clean the bite area with soap and water. If an individual develops a rash or fever, it is recommended to seek medical care immediately to prevent further sequelae.
Enhancing Healthcare Team Outcomes
Lack of familiarity with ACA is a major contributor to proper diagnosis and treatment delays. Thus, ACA should be kept on the differential when evaluating skin lesions on the extremities in elderly patients, especially for those with a history of a tick bite. Collaboration between an interprofessional team (dermatologist, rheumatologist, neurologist, cardiologist) is beneficial for patients with multiorgan involvement.
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