from : The Pathologist's View of Lyme disease
source: Wisconsin Medical Journal 1989;88(11):17-20
authors: Hejka, England, Schmitz, Schell--Madison
"...Skin manifestations
"Quite frequently, patients do not recall being bitten by a tick. Some develop an erythematous (red) papule (small, red, elevated area on the skin, solid and circumscribed; a pimple. Papules often precede vesicular or pustular formation and may appear in erythema multiform, exzema papulosum, prurigo, syphilis, measles, smallpox......from Taber's Cyclopedic Medical Dictionary) within 24 to 48 hours at this bite site which is not the rash of Lyme disease but a transient reaction to a trauma of the tick bite. Infrequently a biopsy is performed on the site and if the tick is still attached and burrowed into the tissue it may appear in stained tissue sections surrounded by inflammatory cells." remember that many times the tick is no bigger than a sesame seed or the period at the end of this sentence. "Microscopic examination may reveal inflammation and disruption of the epidermis along with adjacent epithelial hyperplasia.(3) Cases wherein patients with Lyme disease undergo unrelated operations , during which tissue is removed, are rare, but can be valuable in studying the systemic histopathology of Lyme disease.
"Usually, within thirty days of after exposure, erythema migrans (EM) may develop near the site of the initial tickbite or on the same extremity but may occur in unrelated sites and be multiple.(4) Approximately 70-80% of patients who are bitten by the tick will develope the rash.....Biopsies of the skin lesion shows non-specific inflammation, especially around the blood vessles.
B. burgdorferi has been cultured from these lesions, (5) however, because of the low number of spirochetes present in the tissues and the complexity of the culturing system, it is not a technique sensitive enough to be routinely used in clinical settings...."
"Rarely necrotizing splenitis can be caused by B. burgdorferi. (10).....
"The heart may be a target organ in Lyme disease....
" Lyme arthritis is FREQUENTLY mistaken clinically for rheumatoid arthritis, systemic lupus erythematous, or Reiter's syndrome. Synovial biopsies are probably the most frequent tissue examined microscopically from patients with Lyme disease. The histopathological spectrum ranges from chronic hyperplastic synovitis with effusions to erosive ostearthritis. (20)...
"The disease captures the imagination of physicians, especially in endemic areas such as Wisconsin. Lyme disease is a multisystem disorder with protean manifestations....."

3. Duray PH: The surgical Pathology of human Lyme disease. American Journal of Surgical Pathology 1987;11(suppl 1):47-60.

4. Steer AC, Bartenhagen NH, Craft JE: The early clinical manifestations of Lyme disease. Anaals of Internal Medicine 1983;99,76-82.

5. Berger, et al: Isolation and characterization of the Lyme disease spirochete from the skin of patients with erythema chronicum migrans. Journal of American Academy of Dermatology 1984;13:444-449.

10. Rank EL, Dias SM, HansonJ: Human necrotizing splenitis caused by Borrelia burgdorferi. American Journal of Clinical Pathology 1989;91:493-497.

20. Johnston, Durray PH, Steere AS: Lyme arthritis: spirochetes found in synovial microangiopathic lesions. American Journal of Pathology 1985;118:26-34.


from: Annals of Internal Medicine--Vol. 114--Number 6--March 15, 1991 pg. 490-498
title: Diagnosis of Lyme Disease Based on Dermatologic Manifestations
authors: Malane, MD, et al

"Erythema migrans occurs in 60 to 83 % of patients with Lyme disease (8-10). Classic erythema migrans starts as a red macule or papule at the site of the tick bite, which then expands, forming an erythematous, annular lesion with partial clearing center (11, 42). An erythematous central punctum or a larger macule will often remain at the bite site. Many patients with erythema migrans are unable to recall the tick bite. The lesion is generally found in body areas where ticks characteristically feed. Such areas include those where tight fitting clothing begins (for example at underwear lines ) and interiginous" (superficial inflammation of two skin surfaces taht are in contact) "locations such as the axilla, groin, thigh, and buttocks (11). Ticks infrequently feed on the palms, the soles, or the mucous membranes, Erythema migrans begins approximately 3 to 30 days after a tick bite (11, 12, 42) The inflamed border will migrate cenrifugally over days to weeks. The average size of the lesion is 15 cm, but lesions as large as 68 cm in diameter have been reported (11). Erythema migrans is usually flat; however , the edges may be elevated or indurated (11, 42). Although erythema migrans is usually asymptomatic , burning, prutitus" (itchy)", pain, tenderness, hyperesthesia, or dysesthesia may occur (11, 12, 12, 43). In more than 50% of patients, the lesion is associated with a flu-like illness characterized by fever, myalgia, arthralgias, malaise, fatigue or headache(11, 43). When left untreated, the lesion fades weeks to months later, with an average duration of 1 month (8, 11, 12). On fading there may be residual scaling or pigmentary change in the skin (11, 12)..........
"The histologic findings associated with erythema migans are relatively nonspecific; thus for histopathologic confirmation , the presence of B.burgdoreferi needs to be shown by silver stain, labeled antibody staining or culture(23). Spirochetes are most frequently found in the dermis of the advancing margin of the lesion (34, 45) Histopathologic findings in specimens from the periphery of the lesion include a superficial and deep perivascular lymphocitic infiltrate that may contain plasma cells, histiocytes, and, less commonly mast cells or neutrophils. (11, 42, 43, 45). Histopathologic findings in specimens from the center of the lesion are consistent with a reaction to an arthropod bite, with eosinophils within the dermal infiltrate. Occasionaly vasculitis" (patchy inflammation of walls of small blood vessles)" or vesicular" (having blisters)" changes are also seen(11).
"Other, less classic presentations of the erythema migrans are common. The central area of the lesion may show equal or greater erythema than the periphery(11, 13, 43). A European study (12) found that the homogeneous erythematous lesions persist for shorter duration than those with central clearing. An erythema migrans lesion can have alternating rings of erythema and clearing, thereby creating target configuration(11). Additionally, the central portion of the erythema migrans lesion may show blue discoloration or frank purpura,"(a skin rash resulting from bleeding into the skin from small blood vessles-capillaries; the individual purple spots of the rash are called petechiae.)" induration, "(hardening) "vesiculation," (blistering)"
necrosis," (death of cells in organ or tissue) "or ulceration (11-13, 43, 44, 46) . Uncommonly, petechiae, have also been seen within erythema migrans lesions (46). Lesions may also have different shape or textures. Lesions may appear oval or triangular in shape, especially when they follow the lines of the clevage.
(Langer lines ) or are in intertriginous areas (34, 43, 47). Lesions may also be more linear in configuration, especially when located on the scalp or when expanding on an extremity (11,47). Scaling has been identified occasionally on some lesions (13, 34, 43, 47).....The differential diagnosis of erythema migrans includes cellulitis , tinea, (ringworm) contact dermatitis, fixed drug reaction. granuloma annulare, reaction to an insect bite, or a Brown recluse spider bite (48).

Secondary (Multiple) Erythema Migrans Lesions
"One or more secondary erythema migrans lesions may develop. Secondary erythema migrans can appear within several days to weeks after onset of the initial erythema migrans lesion and has been reported in 6% to 48% of patients with Lyme disease (11, 12, 43). Secondary erythema migrans may result from spirochetemia" (spirochetes in the blood)" or lymphatic spread and subsequent seeding of the skin.
(49). Lesions often occur at sites away from the original lesion, but a single secondary lesion may occur at the site of a primary lesion that has disappeared. When many lesions are present, they can become confluent " (meeting) "or intersecting, forming complicated patterns. The secondary lesions are often similar to the intial erythema migrans lesion, but they tend to lack indurated centers. (11). Secondary lesions are often asymptomatic. If untreated, the lesions usually disappear within a month, but they may persist for months to over a year, or there may be relapses. In patients receiving therapy, secondary lesions resolve over several days (11). The differential diagnosis of secondary erythema migrans includes erythema multiform, erythema annulare cetrifugum, secondary syphilis, erythema marginatum, and drug reaction..."
Acrodermatitis Chronica Atrophicans
"Acrodermatitis Chronica Atrophicans is a unique late complication of Lyme disease, which was first recognized in 1883 (54) . .......It has been reported as the first manifestation of Lyme disease; for example, one asymptomatic patient, on screening had a high serum titer of B. burgdorferi antibodies and he developed acrodermatitis chronica atophicans 4 years later (13, 54, 56)....Classically, there is an intial erythematous or violaceous discoloration in doughy and swollen skin, appearing as plaques or nodules (13, 54). ....The lesion expands and may have a waxing and waning course ((13, 58). This stage will continue for weeks to years before becoming atrophic......There may be hypopigmentation or hyperpignmentation as well as scaling (54, 57). The lesion may be associated with pain, pruritis,"(itching)" hyperesthesias, or paresthesias (55, 57)." (esthesia--from Taber's Cyclopedic Medical Dictionary-- 1. Perception ; feeling; sensation 2. Any disease that affects sensations and perceptions.----para is a prefix meaning near, beside, past, opposite, abnormal, irregular, two like parts-----hyper is a prefix meaning above, excessiive or beyond) "Regional lymphadenopathy," (a disease of the lymph nodes---pathy is a combining form indicating disease.---While I was looking this up I noticed that Taber's 18 th edition has a computer glossary included.) " as well as neurological and musculoskeletal signs or symptoms, may be localized to the same extremity as the acrodermatitis chronica atrophicans lesion (13, 57). An associated sclerotic or fibrotic lesion may be found in patients with acrodermatitis chronica atrophicans (13, 28, 57). The differential diagnosis includes thrombophlebitis, venous insufficiency, eczematous dermatitis, cold injury or aging......

"Fibrotic lesions, such as ulnar (or tibial) bands and ulnar nodules, have been asssociated with acrodermatitis chronica atrophicans lesions....Ulnar (or tibial ) bands are fibrotic, dense, linear bands taht occur in association with atrophic plaques over the respective bones. .......periarticular fibrous nodules ...These nodules can be confused with rheumatoid nodules, gouty tophi, or erythema nodosum, especially if the acrodermatitis achronica atrophicans lesion has gone unnoticed. (13).......

".......Morphea (Localized Scleroderma) and Other Scleradermatous Lesions "Various types of sclerotic lesions, which are characterized by a thickened dermis, develope in about 10% of... patients with acrodermatitis chronica atrophicans and Borrelia lymphocytoma........Sclerodermatous lesions were first reported in association with acrodermatitis chronica atrophicans in the 1930's. The best described of these lesions are those that are both clinically and pathologically identical to morphea (localized scleroderma). Even Morphea lesions that occur in patients without
a history of Borrelia lymphocytoma or acrodermatitis chronica atrophicans may be of spirochetal origin;..........
"Plaque-type morphea" ( from Mosby's Medical, Nursing and Allied Health dictionary.
Morphea--localized scleroderma consisting of patches of yellowish or ivory-colored, rigid, dry, smooth skin. It is more common in females. Also called Addison's keloid, circumscribed scleroderma localized scleroderma.) "manifests as a well-demarcated, indurated, round or
oval plaque with two stages. It begins as an edematous, erythematous lesion that may have a violaceous or lilac tinged border. As the lesion ages, it becomes a sclerotic plaque with a smooth and shiny surface that is white or yellow in the center. The lesions can expand in size and are found on the trunk or extremities. Although they are often painless, they have been associated with dysesthesias, hypoesthesias, and hyperesthesias. Biopsy specimens taken from the early lesion, especially from the violaceous border, show a mixed superficial and deep perivascular lymphohistiocytic infiltrate with plasma cells and occasional eosinophils. The dermis is thickened with sclerosis and hylanization of collagen bundles. As the lesion ages, the dermis becomes more sclerotic, and the inflammatory infiltrate begins to disappear. Morphea may resolve spontaneously after months to years, leaving pigmentary or atrophic changes, or both. Data about treatment are inconsistent. Early lesions and lesions associated with acrodermatitis chronica atrophicans have responded to antibiotics, and some late lesions have STOPPED PROGRESSING when treated.
"Atrophoderma of Pasini and Pierini is rare and probably an atrophic variant of morphea. Spirochetes have been cultured from one lesion. Atrophoderma, a lesion of dermal atrophy progressing to sclerosis, presents as a grey or pigmented lesion with sharp peripheral margins that appear to drop into a depression. Atrophoderma appears most often on the back. A histologic examination done early in the course of the lesion will show a mild diffuse lymphocytic infiltrate and a slight thickening of collagen bundles. As lesions age, the inflammatory infiltrate may disappear
and the thickened collagen bundles may increase, appearing tightly packed.
Data on therapy are not currently available.......
"Conclusion----
"The diagnosis of Lyme disease is based on recognizing the characteristic clinical presentations. Serologic testing is an adjunct to clinical diagnosis.
Primary and secondary erythema migrans, Borrelia lymphocytoma, and acrodermatitis chronica atrophicans are characteristic dermatologic lesions that establish the diagnosis of Lyme diseasse. Less specific cutaneous manifestations of Lyme disease include benign lymphocytic infiltration, morphea, lichen sclerosis et atrophicus, eosinophilic fasciitis, and progressive facial hemiatrophy................Recognizing and treating the cutaneous manifestations of Lyme disease is INVALUABLE for preventing progression of this multisystem infection."

from: California Lyme Disease Symposium 1994
Lyme Disease Resource Center of California
reported by Jean Hubbard

"Dermatologic Manifestations of Lyme Disease------

"Dermatologist Rudy Scrimenti, the first physician to identify EM in the United States, noted that cutaneous manifestations of Lyme disease have served as hallmarks of the disease., but agreed with Dr. Katzel that 'the classical lesion with central clearing and red bands, although most diagnosable and most readily recognizable, is far from being the most common lesion of EM, with triangular lesions being quite common..' .....There is another lesion with varieagated redness throughout, but in the central portion there are blisters or vesicles. Sometimes these become crusted and highly inflammed. When inflammatory changes occur in EM they are always focally placed in the central portion and not throughout the lesion. They will eventually scale, but scaling occurs only in the center and is not a particularly consipicuous feature at the peripheral margins. 90% of the cultures are negative in such lesions, and one of athe reasons is that some of the inflammatory lesions probably show a hypersensitivity reaction to the tick parts, possibly to the tick salivary gland substances......
"There are Lyme disease rashes of sorts not yet documented well in the United States, but present in Europe. These include a reddened breast nipple areola, which is a Lyme borrelial lymphocytoma: this is the most common location in adults, males and females. The most common site in children is the lobe of the ears.; thus far this has not been successfully cultured in the United States. " (this might have changed at this time) " Coalescent papules on the entire rim of the auricle are also compatible with lymphocytoma. There are also lymphocytomas that remain, sometimes for years, after the more typical EM rash resorbs; these do improve with tetracycline and I am SURE I HAVE SEEN THESE IN MY PRACTICE IN WISCONSIN, but thus far I've been unable to obtain a positive culture. The most important alternative diagnosis for such lymphocytomas are malignant lymphoma........"

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