Acrodermatitis Chronica Atrophicans Lesions Research Articles

Peripheral Neuropathy in Acrodermatitis Chronica Atrophicans – Effect of Treatment

Forty‐seven patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA) and with objective neurological and/or neurophysiological findings were followed up after antibiotic treatment with dermatological, serological, neurological and neurophysiological controls. Despite a good therapeutic effect on ACA lesions, specific antibody values and symptoms of irritative nerve lesions, the objective neurological and neurophysiological findings of nerve deficit remained unchanged. There was no progress of neuropathy findings during the follow‐up time. Our interpretation of the results is that the remaining neuropathy signs after treatment of ACA are neurological sequelae and not manifestations of persisting Borrelia infection.

Interstitial granulomatous dermatitis with histiocytic pseudorosettes: A new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA

Background: The cutaneous manifestations of Borrelia burgdorferi infection include an early phase of erythema chronicum migrans and a late stage of acrodermatitis chronica atrophicans lesions. Objective: We describe 11 patients with peculiar cutaneous manifestations and distinctive histopathologic findings as the result of B burgdorferi infection. Methods: Eleven patients with B burgdorferi detected by polymerase chain reaction or polymerase chain reaction enzyme-linked immunosorbent assay in their cutaneous lesions were included in this study. We analyzed clinical data and histopathologic findings in all patients. The inflammatory infiltrate was also immunohistochemically investigated. Results: Most patients showed a peculiar clinical setting of morphea, and a few cases presented the characteristic appearance of erythema chronicum migrans instead of acrodermatitis chronica atrophicans, as would be expected in a late phase of B burgdorferi infection. The histopathologic findings were similar in all cases and consisted of an interstitial inflammatory infiltrate mostly composed of histiocytes dispersed among the collagen bundles of the dermis and focal areas of small pseudorosette formation, characterized by small histiocytes radially disposed around thick collagen bundles. In some cases there were also a few plasma cells intermingled with the histiocytes. Conclusion: Cutaneous lesions with clinical appearance similar to that of morphea and histopathologic features closely resembling those of the interstitial type of granuloma annular may be seen in intermediate-stage cutaneous lesions of B burgdorferi infection. These clinical and histopathologic findings represent a constellation of findings that have not been previously characterized as a cutaneous manifestation of B burgdorferi infection. (J Am Acad Dermatol 2003;48:376-84.)

Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis.

Skin biopsies of 36 patients with erythema migrans and acrodermatitis chronica atrophicans (ACA) before therapy and those of 8 patients after therapy were examined for Borrelia burgdorferi DNA by PCR. Skin biopsies of 27 patients with dermatological diseases other than Lyme borreliosis and those of 10 healthy persons were examined as controls. Two different primer sets targeting 23S rRNA (PCR I) and 66-kDa protein (PCR II) genes were used. PCR was performed with freshly frozen tissue (FFT) and paraffin-embedded tissue (PET). For FFT specimens of erythema migrans, 73% were positive by PCR I, 79% were positive by PCR II, and 88% were positive by combining PCR I and II. For PET specimens, PCR was less sensitive (PCR I, 44%; PCR II, 52%). For FFT specimens of ACA, PCR I was positive for two of five patients and PCR II was positive for four of five patients. B. burgdorferi was cultured from 79% of the erythema migrans specimens but not from any of the ACA lesions. Elevated B. burgdorferi antibodies were detected in sera of 74% of erythema migrans patients and 100% of ACA patients. All urine samples were negative by PCR II, whereas PCR I was positive for 27%. However, hybridization of these amplicons was negative. Sequencing of three amplicons identified nonborrelial DNA. In conclusion, urine PCR is not suitable for the diagnosis of skin borreliosis. A combination of two different primer sets achieves high sensitivity with skin biopsies. In early erythema migrans infection, culture and PCR are more sensitive than serology.

Identification of Three Species of Borrelia burgdorferi Sensu Lato (B. burgdorferi Sensu Stricto, B. garinii, and B. afzelii) Among Isolates from Acrodermatitis Chronica Atrophicans Lesions

In Europe, at least three species of Borrelia are known to be causative agents of Lyme borreliosis: B. burgdorferi sensu stricto, B. garinii, and B. afzelii. Observable differences in the molecular characteristics of the three species have led to speculation that they may also differ in their pathogenic potential and/or tissue tropisms. Several studies have found an association between the chronic skin manifestation of Lyme borreliosis, acrodermatitis chronica atrophicans, and infection by B. afzelii. We sought to find further evidence for such a correlation by studying the genetic profiles of 22 strains of B. burgdorferi sensu lato derived from 21 patients who presented to the University Medical Center, Ljubljana, Slovenia between 1992 and 1995. Strains were isolated in culture from skin biopsies of acrodermatitis chronica atrophicans lesions; in the case of one patient two separate acrodermatitis chronica atrophicans lesions were cultured. All 21 patients had clinically typical lesions with "classic" histopathology and high IgG antibody titers to B. burgdorferi sensu lato. Strains were characterized and typed by 16S ribosomal RNA-specific polymerase chain reaction and determination of their large restriction fragment patterns using pulsed-field gel electrophoresis of MluI-digested genomic DNA. Of the 22 isolates studied, 17 possessed the highly conserved MLa1 pattern characteristic of B. afzelii. The remaining five isolates possessed large restriction fragment patterns that were typical of B. garinii (MLg2, four isolates from three patients) and B. burgdorferi sensu stricto (MLb2, one isolate). The results of 16S ribosomal RNA-specific polymerase chain reaction were concordant with these species designations. These data show that B. afzelii is the predominant, but not the exclusive, etiologic agent of acrodermatitis chronica atrophicans.

A two year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis.

AIM: To compare polymerase chain reaction (PCR) amplification of borrelial DNA and culture isolation of spirochaetes for the diagnosis of Lyme borreliosis by direct detection of Borrelia burgdorferi sensu lato...

Peripheral neuropathy in acrodermatitis chronica atrophicans - a late Borrelia manifestation.

Clinical and/or neurophysiological signs of peripheral neuropathy were found in 64% of 63 consecutive untreated patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA). The neuropathy frequency was significantly higher in the patients than in 30 age- and sex-matched control persons of whom 27% had neuropathy findings. The most common neuropathy in ACA was a symmetric distal sensory polyneuropathy. In a subgroup of patients with localized or asymmetric neuropathy, the changes were found more often in extremities with than without visible ACA lesions. Neuropathy symptoms, most often pain and/or paresthesia, were present in 64% of the patients, compared to in 13% of the control persons. Thus, both symptoms and signs of neuropathy were significantly more frequent in patients with untreated ACA than in control subjects.

Etiology of the acrodermatitis chronica atrophicans lesion in Lyme disease.

Spirochete diversity in acrodermatitis chronica atrophicans lesions in a closely defined central European site was compared to that in the local vector population, in human erythema migrans lesions, and in cerebrospinal fluid by amplifying and sequencing a segment of the gene of outer surface protein A directly from sampled tissues. Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi acutely infect human skin and invade internal tissues. Only B. afzelii, however, is associated with acrodermatitis chronica atrophicans lesions, persisting chronically where the skin has atrophied.

Histopathologic patterns of acrodermatitis chronica atrophicans

In the American literature, the main description of the histopathologic findings in acrodermatitis chronica atrophicans (ACA), including those of fibrous nodules, ulnar bands, and pseudosclerodermatous changes, was made by Montgomery in 1967. 1 It was based on his long experience with ACA and on a study made together with Sullivan in 1945. 2 Montgomery divided the histopathologic changes of ACA into three consecutive stages: acute, inflammatory, and atrophic. These stages overlapped each other without clear-cut boundaries. Concerning the findings in the acute stage, he referred to the early European literature. Montgomery found the inflammatory stage to be the most typical and described it in detail. ACA has also been thoroughly discussed by Benjamowitsch and Maschkilleisson; 3 later, Hardmeier reported on the histopathologic pattern of fibrous nodules associated with ACA and, to a certain extent, also that of ACA itself. 4 In 1986, Åsbrink et al reported on the clinical and histopathologic findings in 32 consecutive patients with clinically and serologically verified ACA. 5 This study has been continued, and an additional 106 untreated patients have been investigated. 6 In 1991 Aberer and co-workers compared the histopathologic findings in biopsies taken from lesions of ACA and morphea. The material consisted of 19 patients with ACA and 40 patients with different kinds of morphea. 7 The following description of the histopathologic pattern of ACA is based on the two previously mentioned investigations, 5,6 which together comprise 138 patients with clinically inflammatory lesions. The inflammatory phase can continue many years and slowly merges into the atrophie stage. Besides typical ACA lesions, 8 patients also had fibrous nodules in the olecranon area, 5 had lichen sclerosus et atrophicus-like lesions, and 3 had scleroderma-like lesions. In the experience of the authors, the histopathologic changes in the inflammatory stage of ACA concern mainly the dermis, but in many cases also extend into the subcutaneous fat tissue. This was the case in more than 70% of the biopsies containing enough subcutaneous tissue to be evaluated.

Clinical manifestations of acrodermatitis chronica atrophicans in 50 Swedish patients

A study was made of 50 consecutive patients with untreated acrodermatitis chronica atrophicans (ACA). In all patients elevated anti-spirochetal antibody titers were found at indirect immunofluorescence and enzyme-linked immunosorbent assays, and histologically biopsies exhibited a dermal lymphocytic infiltrate with a moderate to rich admixture of plasma cells and telangiectases. Nine patients had a history consistent with spontaneously healing erythema chronicum migrans Afzelius (ECMA) on the extremity on which, after 0.5-8 years, ACA lesions developed. Eight patients had a history indicating previous cranial nerve involvement and nine had had periods of severe pains in the cervical or lumbar region. Two patients had developed ECMA, facial palsy and ACA in chronological order. In 15 patients radiographic abnormalities of joints and/or bone tissue were found. Besides ACA lesions, lichen sclerosus et atrophicus- or scleroderma-like lesions were found in six patients. The inflammatory ACA lesions were sometimes discrete and had been overlooked. Joint deformities, sclerotic lesions, diffuse edema or pain were the cardinal symptoms in some patients. The findings indicate that clinical recognition of ACA may be difficult and that a combination of clinical, histopathologic and serologic findings may be necessary to establish the diagnosis. The results are consistent with the concept that ACA is a late manifestation of infection by the same spirochete as causes ECMA and Bannwarth's syndrome.

Acrodermatitis chronica atrophicans--a spirochetosis. Clinical and histopathological picture based on 32 patients; course and relationship to erythema chronicum migrans Afzelius.

The recent discovery that spirochetes transmitted by the tick Ixodes ricinus are involved in the etiology of erythema chronicum migrans Afzelius (ECMA), Bannwarth's syndrome, and acrodermatitis chronica atrophicans (ACA) has thrown new light upon these disorders. Thirty-two patients showing clinical and serological evidence of ACA were investigated. Histologically, constant findings in active ACA lesions were telangiectases and a lymphocytic infiltrate with a moderate to rich admixture of plasma cells. Clinically, besides ACA lesions, lichen sclerosus et atrophicus (LSA)-like lesions were found in five patients. Four of these patients displayed a histopathological picture compatible with LSA. These findings suggest a relationship between ACA and LSA. In six patients spontaneous healing of ECMA was followed by ACA lesions after a latency period of 1-8 years. Six patients reported histories of cranial nerve involvement. Radiography revealed subluxation of joints in hands or feet in six patients, and periosteal thickening in another three patients. The results indicate that ACA may be a late manifestation of infection with the same spirochete that causes ECMA and Bannwarth's syndrome. If untreated, the infection may continue for many years and result in irreversible degenerative lesions.