Excerpt from Acrodermatitis Chronica Atrophicans

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Background

Acrodermatitis chronica atrophicans (ACA) is the third or late stage of European Lyme borreliosis (LB). This unusual, progressive, fibrosing skin process is due to the effect of continuing active infection with Borrelia afzelii. Buchwald first delineated it in 1883; Herxheimer and Hartmann described it in 1902 as a tissue paper–like cutaneous atrophy. It is evident on the extremities, particularly on the extensor surfaces, beginning with an inflammatory stage with bluish red discoloration and cutaneous swelling and concluding several months or years later with an atrophic phase. Sclerotic skin plaques may also develop. Physicians should use serologic and histologic examination to confirm this diagnosis.

Pathophysiology

B afzelii is the predominant, but may not be the exclusive, etiologic agent of ACA. Another genospecies of the Borrelia burgdorferi sensu lato complex, Borrelia garinii, has also been detected.

ACA is the only form of LB in which no spontaneous remission occurs. Its pathophysiology is not yet fully understood. ACA appears to be associated with long-term persistence of Borrelia organisms in the skin; several nonspecific reactions together with a specific immune response may contribute to its manifestations.

The persistence of the spirochetes despite a marked cutaneous T-cell infiltration and high serum antibody titers may be connected with resistance of the pathogen to the complement system; the ability to escape to immunologically protected sites (eg, endothelial cells, fibroblasts); and the ability to change antigens, which may lead to an inappropriate immune response. Lack of protective antibodies, with a narrow antibody spectrum and a weak cellular response with down-regulation of major histocompatibility system class II molecules on Langerhans cells, has been observed in patients with LB.

A restricted pattern of cytokine expression in ACA, including the lack of interferon-gamma, may contribute to its chronicity. Cross-reactive antibody responses could take part in autoimmune damage, but whether autoimmune reactions play any role in the pathogenesis of the disease is unclear. The pathogenic mechanism of atrophic skin changes has also not been clarified. Perhaps periarticular regions are favorite sites because of reduced acral skin temperatures or reduced oxygen pressure.

Frequency

United States

The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.

Despite a high incidence of LB in the United States (varying from 95 cases per 100,000 population in Connecticut to 1250 cases per 100,000 population in Nantucket County, Massachusetts [1996 data]), ACA is not seen in the United States, except in a few European immigrants.

International

The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.

Ixodes scapularis, Ixodes pacificus, and 4 other tick species distributed in North America transmit B burgdorferi sensu stricto, causing EM and LB arthritis.

Tick vectors of B afzelii, the main etiologic agent of ACA (and erythema migrans [EM]), are Ixodes ricinus, Ixodes hexagonus, and Ixodes persulcatus distributed in western and central Europe and in far eastern Europe and Asia. Almost all of these hard tick species may also transmit B garinii, a causative agent of EM and neurologic symptoms of LB.

In Europe, LB with all its dermatologic manifestations occurs in almost all countries, predominantly in the central part of the continent. The annual incidence per 100,000 population varies from 16 cases in France to 120 cases in northeastern Poland and Slovenia and to 130 cases in Austria (1995 data).

The frequency of ACA is about 1-10% of all European patients with LB, varying according to the region of the population sampled. Among the group of patients with skin manifestations of LB observed in Vienna, the ratio of the number of EM cases to ACA cases and to Borrelia lymphocytoma (BL) cases was 30:3:1. This ratio is 170:5:1 in the authors' as-yet-unpublished studies (provided in the group of patients with LB in northeastern Poland).

Because the clinical diagnosis of ACA is much more difficult than that of EM or BL, the condition is often underdiagnosed, and, in fact, the ratio of EM cases to ACA cases may be higher. The total number of cases could increase with increasing frequency of untreated European LB. ACA is probably the most common late and chronic manifestation of the borreliosis in European patients with Lyme disease.

A Bulgarian survey found that borrelial lymphocytoma and ACA were rare (0.3%) (Christova, 2004).

Mortality/Morbidity

The course of ACA is long-standing, lasting from a few to several years, and it leads to extensive flaccid atrophy of the skin and, in some patients, to the limitation of upper and lower limb joint mobility.

• Chronic, difficult-to-treat ulcerations of atrophic skin may develop after minor trauma. Malignant degeneration has rarely been observed; one should not consider ACA to be a precancerous disorder.
• The general status of patients with ACA remains good, though they may experience neurologic and/or rheumatologic signs and symptoms.

Race

ACA is not limited to any one nationality or race. It is much more frequent in whites than in other races, probably because of a far higher exposure to ticks transmitting B afzelii.

Sex

More than two thirds of patients with ACA are women. Among the authors' 19 patients, only 5 were men (Flisiak, 1999).

Age

The disease can occur in any age group, but it is most frequent in adults, usually in their 40s or 50s.

• The youngest of the authors' patients was 26 years; the oldest was 73 years (Flisiak, 1999).
• The mean age of the female group was 54.3 ± 12.8 years; the mean age of the male group was 46.2 ± 6.5 years.
• ACA is rare in adolescents; however, it has been observed in children. A case in a 15-year-old girl was reported by Zalaudek et al in 2005.

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