2.2.10 Acrodermatitis Chronica Atrophicans

In the general European population Lyme borreliosis is > 10: 100,000 per year. In France 9.4, in Poland and Austria up to 130, in Slovenia up to 150 / 100,000. In South Sweden in a population study 63 /100000. All ages can be involved, but adults preferred. Data from Central Europe show that after a tick bite in 2.6 up to 5.6% of subjects develop antibodies against Borrelia sensu latu (seroconversion). The seroprevalence in the younger age is around 7%, in the elderly in males around 24% and in females 16%. In total 0,3 to 1,4% of subjects develop a clinical manifestation of the disease after a tick bite. The manifestation of stage II and III ACA is around 1% (- 3%) and other organ involvement around 3% for neuro-borreliosis, 3% for Lyme arthritis and < 1% for cardiac complications. 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. In Norway, ACA accounts for 5% of all clinical cases of LB, and in northern Italy about 2.5%.

Cutaneous manifestation of chronic Borrelia burgdorferi sensu latu infection leading in a first step to inflammatory edematous changes and in a later step to irreversible atrophy. Concurrent neurological, and/or musculo-skeletal and /or cardiac involvement is common.

Acrodermatitis chronica atrophicans is a late manifestation of a chronic infection with the spirochaetes of the species Borrelia afzelii almost exclusively. The transfer of borrelia spp occurs mostly via the tick sting from Ixodes ricinus.

The most prominent reservoirs are birds, mice, hedgehogs and foxes. Less than 10% of patients report a history of a sting. After an Ixodes nymph or adult arthropod has inserted (no bite!) its hypostoma into the upper dermis it releases some factors to help stabilizing its position and to open vessels and avoiding blood clotting when starting to suck. Because of osmotic balance, saliva with borrelia is first deposited in the skin. The reservoir of borrelia is the intestinal fluid of the Ixodes which is released into the skin in parallel or later.

Borrelia organisms are 20µm long and 3µm thick. They have multiple antigenic structures (853) to which the innate immune system reacts. The most important are the flagellin (endoflagellins up to 12 different structures) and outer surface lipoproteins OspA - G.

The innate immune system reacts i.p. on the local site and the regional lymph node with a strong B-cell production of antibodies. Serological detection is detectable at the 3rd to 4th week. In acrodermatis, late antigens are responsible for maintaining the manifestation: OSP 17, Osp A and B, p30,43,45,58 and p837100. They are detected by immunoblotting for classification and follow-up after therapy. Strong B-cell activation and accumulation of plama cells in situ occur. A persistence of microbes over decades is possible.

The organisms are able to invade endothelial cells, fibroblasts, and Langerhans cells and to survive in collagenous tissue. Antigenic mimicry appears. Whereas in erythema migrans IFN gamma is produced for spirochete killing, in ACA it is missing. Destruction of dermal tissue and its adnexae, nerves and epidermal atrophy is the result.

• ACA stage I: inflammatory-edematous stage with livid doughy swelling.

• ACA stage II: atrophic stage (cigarette paper skin, telangiectases, pigmentary changes). Sclerosis (scleroderma-like collagen changes, ulnar and tibial bands) and fibrous nodules (up to several cm hard, cartilage-like nodules about joints) are slowly developing. Associated may be an allodynia and an axonal peripheral neuropathy (Guillain-Bujadoux-Bannwarth syndrome).

Very often the hands and feet, elbows, knees are involved. Initially the manifestation is unilateral, later symmetrical. Unusual localizations are possible, for example on the breast, which may mimic a cancer.

Early inflammatory edematous and late atrophic stage.

The sedimentation rate is elevated. The first serological step is the ELISA test: borrelia IgG titer raised, sometimes IgM persisting. In the immunoblot as a second step one can see a typical pattern without surface proteins (Osp 17 (p21), Osp A and B) and other persisting antigens (p 30,43,45,58 83,100). If neurological symptoms are present, lumbar punction for liquor serology is necessary.

The epidermis and dermis are smaller and adnexal structures with follicles and sweat glands are missing. An infiltrate mostly rich in plasma cells and additionally lymphomononuclear cells is prominent. No neutrophils or eosinophils in this stage of LB. Collagen and elastic fiber destruction are a rule. Sometimes plama cells accumulate around nerve bundles. In difficult situations of making a clear diagnosis, immunohistochemistry against the microbe can detect the organism in the tissue or a PCR is helpful to detect the infection, but negative DNA results are also seen.

In addition to the soft tissue, muscle atrophy may be seen. Polyneuropathy is detected in 50% of cases. Increased vulnerability of atrophic skin with wounding. Development of plasmocytic B cell lymphomas is reported.

Prevention of re-infection by tick stings.

Treatment according to stage related guideline. First choice systemic antibiotic is doxycycline orally 3 weeks 200 mg / day. Infusions with ceftriaxone are an alternative. Multiple cycles of antibiotic therapy can become necessary. However, no treatment following selological persisting markers should be performed. Lyme borreliosis has a different laboratory profile as compared to a clear cut serological follow-up in syphilis.