Quotes from European Authors
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"Skin is the most frequently involved tissue in Lyme borreliosis, and skin manifesta- tions frequently represent clues for the diagnosis. EM, borrelial lymphocytoma (for- merly lymphadenosis benigna cutis) and ACA are today rated as classic manifestations of Lyme borreliosis. These manifestations were well known as distinct skin disorders long before the discovery of the causative agent [17, 25–27]. In addition, Lyme bor- reliosis may be associated with several other skin manifestations, such as scleroderma circumscripta, lichen sclerosus et atrophicus and cutaneous B cell lymphoma."
"Analysis of the genetic profiles of 22 strains of B. burgdorferi s.l. cultivated from skin biopsies of Slovenian patients with ACA lesions revealed 17 (77%) B. afzelii strains, 4 (18%) B. garinii and 1 (5%) B. burgdorferi s.s., indicating that B. afzelii is the predominant, but not the exclusive, etiologic agent of ACA [91]. This was confirmed later in a larger study. According to Ružić-Sabljić et al., among 74 isolates from the skin of patients with ACA, 89% were B. afzelii, 7% B. garinii and 4% B. burgdorferi s.s. [38]."
"The disease starts with a nonspecific perivascular lymphocytic infiltrate. In early lesions, the epidermis is frequently thinned. The upper and middle portions of the dermis show a band-like and perivascular infiltrate consisting of lymphocytes and plasma cells, often in com- bination with more or less pronounced edema [57]. Dilated blood vessels can be found in the superficial dermis.
Periarticular fibroid nodules seen in some patients with ACA are located in the deeper portions of the reticular cutis extending into the sub- cutaneous fat. Clinically, they resemble rheumatoid nodules, but have a different his- tologic structure with a homogeneous eosinophilic center surrounded by irregular fascicles of collagen typically arranged in an onion-like concentric fashion.
Perivas- cular infiltrates of lymphocytes and plasma cells are present predominantly in the peripheral parts of the lesion, and fibrosis is present. In the late stage of ACA, cutane- ous atrophy with more or less pronounced inflammation is present. The epidermis often has only a few layers of cells. Dilated blood vessels surrounded by lymphocytes and plasma cells can be found in the superficial cutis [57, 92, 93]. In very long-stand- ing atrophic lesions, the inflammatory infiltrates are sparse or may even be absent."
"The onset is insidious, hardly appreciable: mildly bluish-red discoloration of the skin appears (usually on the foot, knee or dorsal part of one of the hands, mostly pronounced over metacarpophalangeal joints) and en- larges very slowly over periods of months to years. The involved region is usually edematous; swelling may occasionally dominate the clinical picture. Initially, the erythema and swelling may vary in intensity. In some patients, the cutaneous manifestations are confined to a heel that is swollen, sometimes discolored and painful.
A common typical sign is that one of the feet (sometimes both) gradually increases in size, and the need for larger shoes arises [96]. After the initial months to years, the edema slowly vanishes and gradually atrophy becomes more and more prominent.
The skin becomes increasingly violaceous, thin and wrinkled, with prominently visible underlying vessels. When exposed to a cold environment, the skin becomes pronouncedly bluish.
The violaceous color also becomes more visible when involved arms or legs are in a dependent position. Healing of damage to the skin is impaired. In some patients, a concomitant migrating erythema, similar to EM, can be seen at the periphery of ACA lesions [96]."
"Up to one fifth of patients may have fibrous indurations in the involved regions [67, 95]; they may be band-like (usually in ulnar or tibial regions) or nodular (most often prepatellary or in the vicinity of the olecranon). The indurations are more frequent in the initial years of the evolution of ACA than in the late phase with pronouncedly atrophic skin.In some patients with ACA, sclerotic lesions develop that are clinically and histo- logically indistinguishable from localized scleroderma (morphea) or lichen sclerosuset atrophicus.
According to Asbrink and Hovmark [81], about 10% of patients with typical inflammatory ACA have sclerotic lesions. In one of the studies from that group, in addition to ACA lesions, lichen sclerosus et atrophicus-like lesions were found clinically in 5 of 32 (16%) examined patients. Four of these patients displayed a histopathologic picture compatible with lichen sclerosus et atrophicus, suggesting a relationship between these 2 skin conditions [93]."
"Peripheral nerves and joints are quite often involved in the regions of affected skin [16, 17, 95]. An association between ACA and peripheral neuropathy was established in systematic studies in the 1960s and 1970s. In these reports, nearly half the patients with ACA showed signs of predominately sensory polyneuropathy, often most pronounced in the limbs, with cutaneous involvement [96, 97]. After the recognition that ACA is a manifestation of borrelial infection, it became obvious that the majority of untreated patients with ACA have some kind of mild (mostly) or moderate neuropa- thy, as indicated by clinical and/or neurophysiologic examination [98, 99]. Peripheral nervous involvement is more frequent in the late phase of ACA. Sensory and motor mononeuropathy or polyneuropathy or patchy dysesthesia may develop at the site of the cutaneous lesions. Patients with ACA quite often complain of hyperesthesia/dys- esthesia, muscle cramps, weakness in the muscles and/or sensations of heaviness, mainly in the affected limb(s)."
"In contrast to peripheral neuropathy, there are far fewer data on CNS involvement in patients with ACA. According to published information, CNS involvement and cerebrospinal fluid (CSF) abnormalities are rare [96].In an investigation of 50 patients with ACA, radiographic examination revealed subluxation and/or luxations of small joints of the hands or feet in 11 (22%) patients; 4 (8%) patients showed periosteal thickening of bones (similar to dactylitis syphilitica in the late phase of syphilis) [95, 96].
The affected joints and bones were usually located underneath the skin lesions. The patients with skeletal involvement had had their dis- ease for a longer period than the patients with skin lesions alone [81, 95, 96]. In 17 of 86 (20%) patients, episodic attacks of joint effusions of a knee were found to have preceded or have occured simultaneously with the ACA lesions [81]. Periarticular manifestations – such as knee or olecranon bursitis, epicondylitis, retro- or subcalcaneal bursitis, and Achilles tendinitis on the same extremity as the cutaneous involvement – have been reported; they usually precede, but sometimes also accompany ACA [81, 100]."
"According to some reports, enlarged regional lymph nodes are a common finding in patients with ACA [101]. Some patients report headaches, myalgia and/or arthral- gia [92]."
"Routine laboratory tests may find mild-to-moderately elevated erythrocyte sedimentation rates, and raised -globulin and C-reactive protein concentrations, but these are usually in normal range and are not of substantial diagnostic help [17, 96]. Diagnosis of ACA can be further supported by the isolation of borreliae from the involved skin; isolation is successful in about one third of patients who have not pre- viously received antibiotics [91]."
"ACA is often overlooked or misinterpreted, not only by patients, but also by their physicians. Frequent visits to the doctor without establishing a proper diagnosis are more often the rule than the exception. Difficulties in recognition are usually the re- sult of limited acquaintance with the disease, but can also be a consequence of atypi- cal clinical features. ACA has many differential diagnoses, which partly depend on the stage of the disease."
"ACA skin lesions on lower extremities are often falsely inter- preted to be a result of vascular insufficiency (chronic venous insufficiency, superfi- cial thrombophlebitis, hypostatic eczema, arterial obliterative disease, acrocyanosis, livedo reticularis, lymphedema, etc.), a consequence of old age (‘old skin’) or chil- blains.
Fibrous nodules are often misinterpreted as rheumatoid nodules and some- times as skin involvement in the course of gout (tophi) or even as erythema nodosum. It is not unusual for patients with ACA to visit their doctor because of difficulties with shoes associated with deformations of joints, or because of dysesthesias, hyperesthe- sias or paresthesias. General physicians and the specialists to whom these patients are quite frequently referred often fail to appreciate ACA skin lesions, do not take them seriously or are not able to associate the skin lesions with the involvement of joints and/or peripheral nervous system [17, 95, 96]."
"ACA should be considered as a possible diagnosis in a patient with bluish-red dis- coloration of a limb with or without swelling and/or atrophy [67]."
"There have been several attempts to demonstrate borreliae in the skin lesions. As reviewed by Mullegger [67] in 2004, spi- rochetes were found by immunohistology or silver staining of lesional tissue from about 20 patients with scleroderma circumscripta and a similar number with lichen sclerosus et atrophicans. Those methods, however, are susceptible to artifacts and in- terpretation faults, and the findings could not be reproduced by other investigators. In the same review, Mullegger [67] reported that PCR studies of lesional skin gave positive results in 21 of 140 scleroderma circumscripta patients and 15 of 40 lichen sclerosus et atrophicans patients in Europe (particularly Germany and Italy) and Japan [106], whereas B. burgdorferi s.l.-specific DNA could not be amplified in any of 98 scleroderma circumscripta and 48 lichen sclerosus et atrophicans patients in the USA [106, 107]."
"The isolation of the causative agent (borreliae) from the lesion is the most reli- able demonstration of the etiology of the process, and indicates that culture-positive scleroderma circumscripta and lichen sclerosus et atrophicans lesions were really caused by B. burgdorferi s.l."
"Sclerotic lesions, which are clinically and histologically indistinguishable from localized scleroderma (morphea) or lichen sclerosus et atrophicus, develop in about 10% of pa- tients with typical inflammatory ACA [93, 96]."