Acrodermatitis chronica atrophicans (ACA) is a late and chronic manifestation of Lyme borreliosis (LB). ACA predominantly involves the distal portions of extremities and is characterized by chronic cutaneous atrophy. Unlike other skin manifestations of Lyme disease, including erythema migrans (EM) and borrelial lymphocytoma (BL), 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 1883 by Buchwald in Germany, and cases were later reported in 1895 in North America. 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. It is transmitted to humans via an Ixodes tick bite. There are 3 skin manifestations of LB: 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 acrodermatitis chronica atrophicans (stage 3) in Europe. Acrodermatitis chronica atrophicans is the most common late and chronic manifestation of LB. 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.
Borrelia is a member of the Spirochaetacea family. There are approximately 20 different genospecies, but only five pose a significant pathogenic risk to humans: B. afzelii, B. garinii, B. bavariensis, B. burgdorferi sensu stricto, and B. spielmanii. Acrodermatitis chronica atrophicans results predominantly from bacterial infection with B. afzelii. However, it can also be caused by European B. burgdorferi sensu stricto or B. garinii.
Acrodermatitis chronica atrophicans predominantly affects women who are 40-70 years of age. ACA is rare in the pediatric population, with few cases reported in children. 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%.
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. 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. If untreated, there is hematogenous spread and development of systemic symptoms.
In ACA, there is a chronic T-cell mediated immune reaction against Borrelia with the presence of CD3+ and CD4+ cells in the dermal infiltrate. Borrelia bind to extracellular matrix proteins, including glycosaminoglycan-binding protein, fibronectin-binding protein, and decorin proteoglycan. They activate metalloproteases and cause degradation of the extracellular matrix. Borrelia also have a high affinity for collagen fibers, which has been demonstrated on electron microscopy. Damage to connective tissues, with the destruction of collagen, leads to fibrosis and dermal atrophy.
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.
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. Acrodermatitis chronica atrophicans is considered to be 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.
In 15% of the patients with ACA, a localized increase of collagen leads to band-like induration with decreased movement of the joints. Peripheral neuropathy can occur in approximately half of the patients, with associated numbness, tingling, or allodynia. Enlargement of the limb with tenosynovitis and dactylitis is a rare occurrence.
The diagnosis of ACA is based on clinical findings and supported by serologic tests (high level of specific Borrelia IgG antibodies). In the majority of the chronic Lyme disease patients, serology is positive for Borrelia IgG antibodies. IgM antibodies against Borrelia are often a false positive in late-stage and thus not useful in diagnosing ACA. 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 in confirming the diagnosis.
The standard management is based on the administration of 1 of the following antibiotics:
The differential diagnosis of ACA depends on the clinical presentation and disease stage. Lesions on the lower extremities are often mistaken as vascular insufficiency (i.e., 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.
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 complete fading of the skin lesion. 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 (i.e., pain, paresthesia).
Acrodermatitis chronica atrophicans 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.
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 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. When walking in wooded areas, individuals should use personal protective measures to keep safe. These include applying repellents, wearing long sleeves, tucking pant legs into socks or long boots, and wearing light-colored clothing to allow ticks to be more readily visible. When returning from the outdoors, it is crucial to change clothing and examine the body for ticks. If a tick is found, individuals should use fine-tipped tweezers to grasp the organism as close to the surface of their skin, 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.
Lack of familiarity with acrodermatitis chronica atrophicans is a major contributor to delay in proper diagnosis and treatment. Thus, ACA should be kept on the differential when evaluating skin lesions on the extremities in elderly patients, and especially for those with a history of a tick bite. In patients with multiorgan involvement, a collaboration between an interprofessional team (dermatologist, rheumatologist, neurologist, cardiologist) is beneficial.
|||Moniuszko-Malinowska A,Czupryna P,Dunaj J,Pancewicz S,Garkowski A,Kondrusik M,Grygorczuk S,Zajkowska J, Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis. Postepy dermatologii i alergologii. 2018 Oct; [PubMed PMID: 30429707]|
|||Scott JD, Presentation of Acrodermatitis Chronica Atrophicans Rashes on Lyme Disease Patients in Canada. Healthcare (Basel, Switzerland). 2020 Jun 4; [PubMed PMID: 32512846]|
|||Sigal LH, Current recommendations for the treatment of Lyme disease. Drugs. 1992 May; [PubMed PMID: 1379147]|
|||Stanek G,Strle F, Lyme borreliosis-from tick bite to diagnosis and treatment. FEMS microbiology reviews. 2018 May 1; [PubMed PMID: 29893904]|
|||Stanek G,Fingerle V,Hunfeld KP,Jaulhac B,Kaiser R,Krause A,Kristoferitsch W,O'Connell S,Ornstein K,Strle F,Gray J, Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2011 Jan; [PubMed PMID: 20132258]|
|||Hofmann H,Fingerle V,Hunfeld KP,Huppertz HI,Krause A,Rauer S,Ruf B, Cutaneous Lyme borreliosis: Guideline of the German Dermatology Society. German medical science : GMS e-journal. 2017; [PubMed PMID: 28943834]|
|||Vasudevan B,Chatterjee M, Lyme borreliosis and skin. Indian journal of dermatology. 2013 May; [PubMed PMID: 23723463]|
|||McGinley-Smith DE,Tsao SS, Dermatoses from ticks. Journal of the American Academy of Dermatology. 2003 Sep; [PubMed PMID: 12963900]|
|||Bhate C,Schwartz RA, Lyme disease: Part I. Advances and perspectives. Journal of the American Academy of Dermatology. 2011 Apr; [PubMed PMID: 21414493]|
|||Hubálek Z,Halouzka J, Distribution of Borrelia burgdorferi sensu lato genomic groups in Europe, a review. European journal of epidemiology. 1997 Dec; [PubMed PMID: 9476827]|
|||Glatz M,Resinger A,Semmelweis K,Ambros-Rudolph CM,Müllegger RR, Clinical spectrum of skin manifestations of Lyme borreliosis in 204 children in Austria. Acta dermato-venereologica. 2015 May; [PubMed PMID: 25366035]|
|||Wolgemuth CW, Flagellar motility of the pathogenic spirochetes. Seminars in cell [PubMed PMID: 26481969]|
|||Vig DK,Wolgemuth CW, Spatiotemporal evolution of erythema migrans, the hallmark rash of Lyme disease. Biophysical journal. 2014 Feb 4; [PubMed PMID: 24507617]|
|||Tee SI,Martínez-Escanamé M,Zuriel D,Fried I,Wolf I,Massone C,Cerroni L, Acrodermatitis chronica atrophicans with pseudolymphomatous infiltrates. The American Journal of dermatopathology. 2013 May; [PubMed PMID: 23147352]|
|||Buechner SA,Rufli T,Erb P, Acrodermatitis chronic atrophicans: a chronic T-cell-mediated immune reaction against Borrelia burgdorferi? Clinical, histologic, and immunohistochemical study of five cases. Journal of the American Academy of Dermatology. 1993 Mar; [PubMed PMID: 8095272]|
|||Parveen N,Leong JM, Identification of a candidate glycosaminoglycan-binding adhesin of the Lyme disease spirochete Borrelia burgdorferi. Molecular microbiology. 2000 Mar; [PubMed PMID: 10712702]|
|||Brissette CA,Bykowski T,Cooley AE,Bowman A,Stevenson B, Borrelia burgdorferi RevA antigen binds host fibronectin. Infection and immunity. 2009 Jul; [PubMed PMID: 19398540]|
|||Guo BP,Norris SJ,Rosenberg LC,Höök M, Adherence of Borrelia burgdorferi to the proteoglycan decorin. Infection and immunity. 1995 Sep; [PubMed PMID: 7642279]|
|||de Koning J,Tazelaar DJ,Hoogkamp-Korstanje JA,Elema JD, Acrodermatitis chronica atrophicans: a light and electron microscopic study. Journal of cutaneous pathology. 1995 Feb; [PubMed PMID: 7751475]|
|||Müller KE, Damage of collagen and elastic fibres by borrelia burgdorferi - known and new clinical and histopathological aspects. The open neurology journal. 2012; [PubMed PMID: 23986790]|
|||Kempf W,Kazakov DV,Hübscher E,Gugerli O,Gerbig AW,Schmid R,Palmedo G,Kutzner H, Cutaneous borreliosis associated with T cell-predominant infiltrates: a diagnostic challenge. Journal of the American Academy of Dermatology. 2015 Apr; [PubMed PMID: 25617014]|
|||Zambrano MC,Beklemisheva AA,Bryksin AV,Newman SA,Cabello FC, Borrelia burgdorferi binds to, invades, and colonizes native type I collagen lattices. Infection and immunity. 2004 Jun; [PubMed PMID: 15155615]|
|||Yssel H,Shanafelt MC,Soderberg C,Schneider PV,Anzola J,Peltz G, Borrelia burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis. The Journal of experimental medicine. 1991 Sep 1; [PubMed PMID: 1831490]|
|||Grab DJ,Kennedy R,Philipp MT, Borrelia burgdorferi possesses a collagenolytic activity. FEMS microbiology letters. 1996 Oct 15; [PubMed PMID: 8870250]|
|||Leslie TA,Levell NJ,Cutler SJ,Cann KJ,Smith ME,Wright DJ,Gilkes JJ,Robinson TW, Acrodermatitis chronica atrophicans: a case report and review of the literature. The British journal of dermatology. 1994 Nov; [PubMed PMID: 7999602]|
|||Zajkowska J,Czupryna P,Pancewicz SA,Kondrusik M,Moniuszko A, Acrodermatitis chronica atrophicans. The Lancet. Infectious diseases. 2011 Oct; [PubMed PMID: 21958583]|
|||Müller DE,Itin PH,Büchner SA,Rufli T, Acrodermatitis chronica atrophicans involving the face. Evidence for Borrelia burgdorferi infection confirmed by DNA amplification. Dermatology (Basel, Switzerland). 1994; [PubMed PMID: 7873838]|
|||Kristoferitsch W,Sluga E,Graf M,Partsch H,Neumann R,Stanek G,Budka H, Neuropathy associated with acrodermatitis chronica atrophicans. Clinical and morphological features. Annals of the New York Academy of Sciences. 1988; [PubMed PMID: 2847621]|
|||Molka A,Jachiet M,Lepelletier C,de Masson A,Bagot M,Bouaziz JD, Asymetric red-blue hypertrophic hand and tenosynovitis due to acrodermatitis chronica atrophicans. Rheumatology (Oxford, England). 2019 Apr 1; [PubMed PMID: 30239931]|
|||Levy E,Morruzzi C,Barbarini A,Sordet C,Cribier B,Jaulhac B,Lipsker D, Clinical images: toe dactylitis revealing late Lyme borreliosis. Arthritis and rheumatism. 2012 Apr; [PubMed PMID: 22275216]|
|||Kaufman LD,Gruber BL,Phillips ME,Benach JL, Late cutaneous Lyme disease: acrodermatitis chronica atrophicans. The American journal of medicine. 1989 Jun; [PubMed PMID: 2729343]|
|||Steere AC,Strle F,Wormser GP,Hu LT,Branda JA,Hovius JW,Li X,Mead PS, Lyme borreliosis. Nature reviews. Disease primers. 2016 Dec 15; [PubMed PMID: 27976670]|
|||Ljøstad U,Mygland Å, Chronic Lyme; diagnostic and therapeutic challenges. Acta neurologica Scandinavica. Supplementum. 2013; [PubMed PMID: 23190290]|
|||Flisiak R,Pancewicz S, [Diagnostics and treatment of Lyme borreliosis. Recommendations of Polish Society of Epidemiology and Infectious Diseases]. Przeglad epidemiologiczny. 2008; [PubMed PMID: 18536243]|
|||Pancewicz SA,Garlicki AM,Moniuszko-Malinowska A,Zajkowska J,Kondrusik M,Grygorczuk S,Czupryna P,Dunaj J, Diagnosis and treatment of tick-borne diseases recommendations of the Polish Society of Epidemiology and Infectious Diseases. Przeglad epidemiologiczny. 2015; [PubMed PMID: 26233093]|
|||Asbrink E,Brehmer-Andersson E,Hovmark A, Acrodermatitis chronica atrophicans--a spirochetosis. Clinical and histopathological picture based on 32 patients; course and relationship to erythema chronicum migrans Afzelius. The American Journal of dermatopathology. 1986 Jun; [PubMed PMID: 3728879]|
|||Leverkus M,Finner AM,Pokrywka A,Franke I,Gollnick H, Metastatic squamous cell carcinoma of the ankle in long-standing untreated acrodermatitis chronica atrophicans. Dermatology (Basel, Switzerland). 2008; [PubMed PMID: 18607109]|
|||Bhate C,Schwartz RA, Lyme disease: Part II. Management and prevention. Journal of the American Academy of Dermatology. 2011 Apr; [PubMed PMID: 21414494]|