eISSN: 2299-0046
ISSN: 1642-395X
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
Current issue Archive Manuscripts accepted About the journal Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
vol. 35
Original paper

Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis

Anna Moniuszko-Malinowska, Piotr Czupryna, Justyna Dunaj, Sławomir Pancewicz, Adam Garkowski, Maciej Kondrusik, Sambor Grygorczuk, Joanna Zajkowska

Adv Dermatol Allergol 2018; XXXV (5): 490-494
Online publish date: 2018/07/19
Article file
- Acrodermatitis.pdf  [0.18 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Lyme borreliosis (LB) in Europe is caused by a genospecies of the Borrelia burgdorferi sensu lato complex. There are three skin manifestations of LB: erythema migrans (EM), borrelial lymphocytoma (BL), and acrodermatitis chronica atrophicans (ACA) [1].
In Europe, LB with all its dermatologic manifestations occurs in almost all countries, predominantly in the central part of the continent. The annual incidence ranges from 9.4 cases per 100,000 population in France to 120 cases per 100,000 population in north-eastern Poland, 130 cases per 100,000 population in Austria and 155 cases per 100,000 population in Slovenia [2–4].
The overall prevalence of ACA in all European patients with LB is about 1–10%, depending on the region. For example, in Bulgaria, both BL and ACA account for 0.3% of LB cases [5]. In Norway, ACA accounts for 5% of all clinical cases of LB [6], and in northern Italy – 2.5% [7].
The diagnosis of ACA is much more difficult than that of EM or BL as the clinical manifestations of ACA may vary. Acrodermatitis chronica atrophicans is probably the most common late and chronic manifestation of the LB seen in European patients.


The objectives of the study were to verify human cases of ACA, to analyze their epidemiological data, and to investigate the effects of treatment of patients from the Podlaskie region of Poland, considered as endemic for tick-borne diseases.

Material and methods

Nine patients (5 women, 4 men; mean age: 58.7 ±14.3 years-old, 4 (44%), inhabitants of cities) with ACA were included in the study. All patients were tested for anti B. burgdorferi antibodies of the IgM and IgG class by ELISA (Borrelia recombinant IgG and IgM High Sensitivity, Biomedica, Austria). Results > 11 BBU/ml in the IgM and IgG classes were considered positive.
The studies have been approved by the ethics committee of the Medical University of Bialystok, Poland.
In all cases, results were confirmed by Western blot testing (Biomedica, Austria). In all patients, the histopathological examination of skin samples was performed.
From 8 patients, skin biopsy samples of 3 mm in diameter were taken and examined for the presence of B. burgdorferi s.l. DNA by nPCR (nested PCR). After collection, skin biopsy samples were placed in aseptic rounded-bottom tubes and frozen or prepared fresh. All skin biopsies were cut into smaller parts with stainless steel knife-edge and covered with a maximum of 80 µl PBS buffer.

DNA extraction

DNA from skin biopsies was extracted by using a Qiagen DNeasy Blood and Tissue Mini kit according to the manufacturer’s instructions. Purified DNA (100 µl) was then frozen at –20°C before amplification.

PCR protocol for Borrelia burgdorferi s.l.

A fragment of the fla gene, the specific DNA sequence encoding flagellin was used for B. burgdorferi s.l. detection in “one tube” nested PCR. The Borrelia burgdorferi PCR kit (GeneProof, Czech Republic) for in vitro diagnostics was used for this purpose, minimizing non-specific reactions and maximizing sensitivity because of the “hot start” technology employed. Possibility of PCR inhibition is prevented by addition of internal control into the reaction mix. The risk of contamination is prevented by using uracil-DNA-glycosylase (UDG). 4 µl of the template DNA isolates was added to 36 µl of the MasterMix for final reaction mix volume of 40 µl. The course of the reaction in accordance with the manufacturer’s instructions was performed on the SensoQuest LabCycler (SensoQuest, Germany) with authors’ own modifications. Nested PCR was performed according to the following amplification program: UDG decontamination, initial denaturation at 96°C for 10 min, first amplification for 30 cycles (denaturation at 96°C for 20 s, annealing at 68°C for 20 s, extension at 72°C for 40 s), second amplification for 45 cycles (denaturation at 96°C for 20 s, annealing at 54°C for 20 s, extension at 72°C for 30 s) and final extension at 72°C for 2 min. The samples were cooled at +4°C.
The PCR products were separated on 2% agarose gel (Sigma-Aldrich, Germany) with the addition of ethidium bromide (5 µg/ml; Syngen, USA) at 80 V for 80 min. The results of the PCR were viewed under UV light (UV to Gel Logic System 100 (Kodak Imaging System, Inc., USA). Probes with the PCR product of the size of 276 base pairs (bp) were regarded positive. The internal control had a size of 420 bp. For precise detection of B. burgdorferi s.l. fla, amplicons and internal control molecular weight marker (M100-500-Blirt S.A. Poland) was used.


Eight (88%) of our patients remembered a tick bite. Five (55%) patients had been previously treated with antibiotics because of EM. In 5 (56%) cases, this was a job-related disease. The duration of symptoms ranged from 2 months to 2 years. In 7 (77%) patients, skin lesions were localized on the lower limbs. Two patients had co-existing skin lesions in a non-typical body area – abdomen (Figures 1–6). Six (66%) patients suffered from muscle and 6 (66%) from joint pain. In 1 patient, scleroderma and in 3 (33%) patients, diabetes mellitus was diagnosed as concomitant diseases.
In all patients, ELISA in the IgG class was positive (mean titer: 90.5 ±9.1 BBU/ml). All results were confirmed by Western blot. Histopathological examination revealed features typical of ACA: infiltration of lymphocytes, histiocytes and plasma cells, prominent vascular channels together with telangiectasia, atrophy of the dermis and subcutis, epidermal atrophy and loss of rete ridges, which confirmed the diagnosis.
Borrelia burgdorferi s.l. DNA was detected in 25% of the skin biopsy specimens. Detailed characteristics of patients is presented in Table 1.
Laboratory tests (blood morphology, aminotransferases activity, creatinine concentration, C-reactive protein (CRP) concentration) revealed no abnormalities.
All patients were treated with third-generation cephalosporin (ceftriaxone 2 g/day) for 28 days (according to Polish guidelines). The outcome of treatment varied. In 5 cases, the changes disappeared completely (after 1 to 6 months), in others faded, but skin thinning and discoloration of bluish pink remained (Table 1). No side effects of antibiotic therapy were observed.


Acrodermatitis chronica atrophicans is a late and long-lasting form of LB, which may be present for many years. It is characterized by red or bluish-red lesions and leads to extensive flaccid atrophy of the skin, which becomes more and more prominent. Fibroid nodules may develop over bony prominences and sclerodermic lesions may develop in atrophic skin areas [8]. It may limit movement of upper and lower limb joints. ACA is most commonly located on extremities, although it may affect other skin areas, such as the face [9]. In two of our patients, ACA was located in the abdominal area.
According to the literature, women are more predisposed to ACA (women are more than two thirds of patients) [7, 10]. This tendency was also observed in our study. Acrodermatitis chronica atrophicans can occur in any age group but it is most common in adults, mainly those in their 40-ties or 50-ties and it occurs only rarely in children [11, 12].
Acrodermatitis chronica atrophicans may develop 6 months to 8 years after a tick bite [13]. In our study, the shortest time since the tick bite reported by a patient was 300 days, and the longest was 10 years.
Patients with ACA are usually in a good general condition, though they may experience rheumatologic or neurologic symptoms such as polyneuropathy (typically pain, paresthesia or both). According to the literature, neuropathy symptoms are evident in more than one half of the patients with ACA [13]. We have not observed any neurological symptoms, however 66% of our patients experienced joint pain and muscle pain.
According to the case definition by Stanek et al., the diagnosis of ACA is based on a typical clinical picture, followed by serological tests (high level of specific IgG antibodies), and histological examination. Additionally, detection of B. burgdorferi by culture or PCR from the skin biopsy helps in diagnosis [4]. All our patients fulfilled the diagnostic criteria for ACA. Moreover, in 25% we detected DNA of B. burgdorferi in the skin biopsy.
The ACA lesion has a typical histological appearance with telangiectasias, patchy or band-like lymphocytic and plasma cell infiltrates. Various degrees of atrophy may be observed [4]. According to the recent research, cutaneous borreliosis can histopathologically manifest with a T cell-rich infiltrate mimicking cutaneous T-cell lymphocytoma [14, 15].
The differential diagnosis of ACA depends on the stage of the disease. ACA skin lesions on lower extremities are often misinterpreted as vascular insufficiency (e.g. chronic venous insufficiency, superficial thrombophlebitis, hypostatic eczema, arterial obliterative disease), acrocyanosis, livedo reticularis, lymphedema, a consequence of old age or chilblains. Fibrous nodules may be mistaken for rheumatoid nodules, gout or erythema nodosum [4].
A recent study by Brandt et al. has proved that PCR assays targeting ospA and ospC genes might be helpful in differential diagnosis as the main cause of ACA is B. afzelii, serotype 2, osp C groups Af5, Af2 and Af6 [15].
The standard treatment is based on antibiotic therapy with 1 of the following drugs: with amoxicillin 3 × 500–1000 mg p.o. for 14–28 days, doxycycline 2 × 100 mg or 1 × 200 mg p.o. for 14–28 days, ceftriaxone 1 × 2000 mg i.v. for 14–28 days, cefotaxime 3 × 2000 mg i.v. for 14–28 days, or Penicillin G 3–4 MU every 4 h i.v. for 14–28 days [16, 17]. As a rule, the outcome of treatment is good, especially if the acute inflammatory stage of ACA is treated adequately. The therapeutic outcome is difficult to assess in patients with the chronic atrophic phase, in which many changes are only partially reversible. All our patients were treated with third-generation cephalosporin. Response to 28 days third-generation cephalosporin therapy varied from partial dissolving of the lesion to complete fading.
Acrodermatitis chronica atrophicans may lead to ulcerations or bacterial superinfections [18]. It is also considered a risk factor for cancer development. We have not observed any complications in our patients.
Summing up, diagnosis of ACA is in most cases delayed as the patients do not report serious complaints and the disease usually develops many years after the tick bite. Causative treatment should be implemented as early as possible to prevent irreversible cutaneous damage.


Despite raising awareness of LB, late forms of the disease such as ACA are still observed. Skin lesions in ACA may be located in non-characteristic areas, e.g. abdominal skin and require serological and histopathological confirmation. As the symptoms are not irritating or painful, patients usually do not seek medical attention. The effect of antibiotic treatment varies.

Conflict of interest

The authors declare no conflict of interest.


1. Stanek G, Strle F. Lyme disease – European perspective. Infect Dis Clin N Am 2008; 22: 327-39.
2. Letrilliart L, Ragon B, Hanslik T, Flahault A. Lyme disease in France: a primary care-based prospective study. Epidemiol Infect 2005; 133: 935-42.
3. Rizzoli A, Hauffe H, Carpi G, et al. Lyme borreliosis in Europe. Euro Surveill 2011; 7: 16 pii: 19906.
4. Stanek G, Fingerle V, Hunfeld KP, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect 2011; 17: 69-79.
5. Christova I, Komitova R. Clinical and epidemiological features of Lyme borreliosis in Bulgaria. Wien Klin Wochenschr 2004; 116: 42-6.
6. Nygård K, Brantsaeter AB, Mehl R. Disseminated and chronic Lyme borreliosis in Norway, 1995–2004. Euro Surveill 2005; 10: 235-8.
7. Stinco G, Ruscio M, Bergamo S, et al. Clinical features of 705 Borrelia burgdorferi seropositive patients in an endemic area of Northern Italy. Sci World J 2014; 4: 414505.
8. Zajkowska J, Czupryna P, Pancewicz SA, et al. Acrodermatitis chronica atrophicans. Lancet Infect Dis 2011; 11: 800.
9. Müller DE, Itin PH, Büchner SA, Rufli T. Acrodermatitis chronica atrophicans involving the face. Evidence for Borrelia burgdorferi infection confirmed by DNA amplification. Dermatology 1994; 189: 430-1.
10. Strle F, Wormser GP, Mead P, et al. Gender disparity between cutaneous and non-cutaneous manifestations of Lyme borreliosis. PLoS One 2013; 30: e64110.
11. Andres C, Ziai M, Bruckbauer H, et al. Acrodermatitis chronica atrophicans in two children. Int J Dermatol 2010; 49: 180-3.
12. Zalaudek I, Leinweber B, Kerl H, Müllegger RR. Acrodermatitis chronica atrophicans in a 15-year-old girl misdiagnosed as venous insufficiency for 6 years. J Am Acad Dermatol 2005; 52: 1091-4.
13. Leslie TA, Levell NJ, Cutler SJ, et al. Acrodermatitis chronica atrophicans: a case report and review of the literature. Br J Dermatol 1994; 131: 687-93.
14. Kempf W, Kazakov DV, Hübscher E, et al. Cutaneous borreliosis associated with T cell-predominant infiltrates: a diagnostic challenge. J Am Acad Dermatol 2015; 72: 683-9.
15. Brandt FC, Ertas B, Falk TM, et al. Histopathology and immunophenotype of acrodermatitis chronica atrophicans correlated with ospA and ospC genotypes of Borrelia species. J Cutan Pathol 2015; 42: 674-92.
16. Flisiak R, Pancewicz S. Diagnostics and treatment of Lyme borreliosis. Recommendations of Polish Society of Epidemiology and Infectious Diseases. Przegl Epidemiol 2008; 62: 193-9.
17. Pancewicz SA, Garlicki AM, Moniuszko-Malinowska A, et al. Diagnosis and treatment of tick-borne diseases recommendations of the Polish Society of Epidemiology and Infectious Diseases. Przegl Epidemiol 2015; 69: 309-16, 421-8.
18. Leverkus M, Finner AM, Pokrywka A. Metastatic squamous cell carcinoma of the ankle in long-standing untreated acrodermatitis chronica atrophicans. Dermatology 2008; 217: 15-8.
Copyright: © 2018 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe