Lyme disease_0613 Derm Look 1
Morphea_0613 Derm Look 2
A woman, aged 41 years, complained of a rash on her right posterior axilla. The lesion was associated with a mild burning sensation, but no pruritus or pain was reported. The woman had been hiking while on vacation in Connecticut two weeks earlier. A few days after the hike, her husband removed a tick attached to her right axilla. The eruption developed the following week. She had no systemic complaints. Physical examination revealed an erythematous annular plaque that had a bull’s-eye appearance.
A man, aged 36 years, presented with a rash on his left flank and abdomen. The rash began three months earlier as an erythematous plaque that seemed to be enlarging. Most recently, the man noticed new enlarging lesions on the left abdomen. There was no associated pain or pruritus. No prior treatment had been initiated. Review of systems was otherwise negative. On physical examination, erythematous, slightly edematous, indurated plaques with a peripheral lilac border in some areas were appreciated on the left flank and abdomen.
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In the 1970s, a physician named Steere was asked to investigate an outbreak described as a pediatric type of arthritis preceded by erythema migrans. The outbreak happened around Lyme, Conn., and thus Lyme disease was recognized. In the 1980s, Burgdorferi isolated a new spirochete from erythema migrans that became known as Borrelia burgdorferi. Soon thereafter, it was found that B. burgdorferi was transmitted by such various species of Ixodes ticks as I. scapularis, I. pacificus and I. ricinus.
Lyme disease has a global distribution, and infection occurs most often between May and November, with a peak incidence in June and July. In the United States, cases are most often seen in the Northeast, Midwest, and certain areas of the West Coast. The 10 most affected states are Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin.1
At least 20,000 cases of Lyme disease occur each year in the United States; however, due to underreporting and misdiagnosis, the actual number may be as high as 60,000 to 100,000.
The natural hosts for Ixodes ticks are white-footed mice and white-tailed deer. I. scapularis is the principal vector for cases seen in the northeastern and central United States and in Canada. I. pacificus, as the name implies, is seen more commonly on the Pacific coast. Not all individuals who have been bitten by an Ixodes tick or who have positive serologic tests for B. burgdorferi develop Lyme disease.
The risk of contracting acute Lyme borreliosis in areas endemic for the disease has been estimated to be only 1% of those who are bitten by the tick,2 perhaps owing to the fact that the tick must be attached for at least 24 hours.
After an Ixodes tick bite, the Borrelia organisms enter the body, and spirochetal lipoproteins trigger an innate immune response. Type 1 helper T-cells respond to the invader by activating the adaptive immune system, causing T-cells and B-cells to facilitate the synthesis of autoantibodies to different antigens presented by B. burgdorferi.
The pathogen counterstrikes by resisting macrophage elimination and disseminating throughout the body. The organism attaches itself to areas the human immune system will not strike, such as brain and epithelial cells. It also uses intracellular junctions to penetrate into the cytoplasm and induce production of tumor necrosis factor-α.
The early localized disease occurs three to 32 days (median seven days) after the tick bite and is characterized by erythema migrans, an annular erythematous plaque that spreads centrifugally. The center of the plaque may be a lighter color or have a bull’s-eye appearance, and the overall diameter is usually >5 cm. The lesion favors the trunk, popliteal fossa, axilla and groin.
Some patients may complain of a burning sensation, but rarely is it pruritic or painful. If left untreated, the lesion usually lasts less than six weeks. In approximately 25% of patients, multiple lesions may be present due to multiple tick bites or disseminated disease. Disseminated lesions are often less pronounced and smaller in size and usually appear days to weeks after the initial erythema migrans.3
Influenza-like symptoms may be seen. Approximately 60% of the patients with erythema migrans who are not treated will develop arthritis, 10% will develop a neurologic complication, and 5% will develop a cardiac manifestation.4 Acrodermatitis chronica atrophicans is another indicator of late-stage Lyme borreliosis and is mainly seen in Europe.
Histologic examination is often nonspecific. Most cases demonstrate a superficial and deep perivascular and interstitial infiltrate of lymphocytes, plasma cells and eosinophils. With the help of a Warthin-Starry stain, spirochetes may be seen in the upper dermis.
Erythema migrans may be misdiagnosed as an arthropod assault, erysipelas, cellulitis, urticaria, allergic contact dermatitis, morphea, sarcoidosis, borderline or tuberculoid leprosy, nonpigmented fixed drug eruption, erythema multiforme, erythema annulare centrifugum, tumid lupus erythematosus, granuloma annulare, tinea corporis, syphilis, pityriasis rosea, psoriasis or erythema gyratum repens.
To properly distinguish between Lyme disease and other entities, attempt to isolate B. burgdorferi from tissue or fluids. Culture and polymerase chain reaction analysis are specific but not sensitive and not available in most areas.
The more commonly employed detection method is confirmation of anti-Borrelia antibodies via enzyme-linked immunosorbent assay followed by Western blotting. It should be noted that the Western blot method has a high false-negative rate because the peak immunoglobulin M response occurs three to six weeks after the infection, and most patients present prior to this time.
Such preventive measures as personal avoidance strategies and inspecting for ticks after returning from outdoor activities are worthwhile in tick-infested areas. The treatment of choice for adults and children aged 8 years or older is doxycycline 100 mg by mouth b.i.d. for 14 to 21 days.
Amoxicillin 500 mg (or cefuroxime [Ceftin] 500 mg) by mouth b.i.d. for 14 to 21 days is an alternative treatment for pregnant women and children younger than age 8 years. Although treatment is not recommended for all tick bites, a single 200-mg dose of doxycycline taken within 72 hours of an I. scapularis tick bite is effective at preventing the development of Lyme borreliosis.5
Lyme disease is rarely fatal, and prognosis is excellent with proper treatment. However, it is very important to follow patients to make sure treatment is successful and that no further sequelae of the disease develop.
The patient in this case was treated with doxycycline 100 mg by mouth b.i.d. for 21 days. No signs of disease sequelae were noted on her follow-up visit.
This patient was diagnosed with morphea, also known as localized scleroderma. Scleroderma is an inflammatory condition of the dermis and subcutaneous fat that is ultimately characterized by diffuse, hard, smooth, and immobile scarlike plaques.
There are both cutaneous and systemic types of scleroderma. Cutaneous types are usually asymmetric with a patchy or linear distribution and do not involve internal organs. These types include localized morphea, morphea-lichen sclerosus et atrophicus overlap, generalized morphea, atrophoderma of Pasini and Pierini, pansclerotic morphea, morphea profunda, nodular or keloid morphea, and linear scleroderma.
Systemic types of scleroderma begin as symmetric digital sclerosis that extends proximally toward the trunk. They are usually associated with Raynaud’s phenomenon, and there is involvement of internal organs. Systemic scleroderma includes CREST syndrome and progressive systemic sclerosis.
The term scleroderma is derived from the Greek words skleros, meaning hard, and derma, meaning skin. The history of morphea dates back to 400 b.c., when Hippocrates first described a condition with thickening of the skin. A survey conducted in Olmstead County, Minn., is believed to be one of the most extensive population-based studies of morphea.6 This study showed an incidence of 27 per million people and a prevalence that increases with age. The disease favors women over men by a ratio of 2.6 to 1, with the exception of linear morphea, which does not demonstrate gender preference.
The exact pathogenesis of morphea remains unknown. However, sclerosis of the skin is thought to involve three major components: (1) vascular damage; (2) activated T-cells (which produce interleukin 4 and transforming growth factor-β); and (3) altered connective tissue production by fibroblasts.
An increased prevalence of certain autoantibodies has also been demonstrated, including single-strand DNA (more often in linear morphea), antifibrillin 1, antiphospholipid, antihistone, antitopoisomerase IIα, and antinuclear antibody (more common in juvenile linear morphea or adult generalized morphea). Unfortunately, the trigger for sclerosis remains unknown. It is hypothesized that local triggers in the skin may cause morphea, whereas generalized trauma may lead to systemic sclerosis.
One intensively investigated trigger was B. burgdorferi, the pathogen responsible for Lyme disease and erythema migrans. Researchers focused on B. burgdorferi as a triggering agent because the progression of the erythematous plaque in morphea and erythema migrans is similar, and some cases of morphea had improved following administration of penicillin. Originally, studies isolated B. burgdorferi from the urine and/or skin of some patients with morphea, and messenger RNA specific for Borrelia was appreciated in several.7,8 However, larger subsequent studies have shown no such correlation.9
This article focuses on the clinical features of plaque-type morphea, the most common variant. Lesions begin as erythematous edematous plaques that become sclerotic and expand centrifugally to a diameter of approximately 2 cm to 15 cm. Active lesions have a lilac border, whereas inactive lesions become hyperpigmented. Hair follicles and sweat glands are frequently lost.
Patients may complain of pruritus; however, this is more likely a result of the overlying xerosis rather than being a true manifestation of morphea. Lesions, usually located on the trunk, can be multiple and asymmetric and may enlarge significantly or remain stable in size.
On low-power microscopic examination, thickening of the dermis will give the specimen a squared-off appearance. In the acute phase, a perivascular lymphocytic infiltrate with plasma cells is appreciated most prominently at the junction of the dermis and subcutaneous fat.
In later stages, the collagen is thickened, and inflammation may be minimal. The thickened collagen bundles eventually replace the subcutaneous tissue, causing the eccrine glands to appear trapped within the mid-portion of the thickened dermis. At this stage, pilosebaceous units are usually absent.
The differential diagnosis of morpheaform skin lesions includes graft-versus-host disease, lipodermatosclerosis, sclerosis at injection sites, radiation-induced morphea, chemical/toxin exposures, porphyria, Winchester syndrome, eosinophilia-myalgia syndrome, eosinophilic fasciitis, congenital fascial dystrophy, progeria, scleredema, scleromyxedema, and keloids/hypertrophic scars.
Although inflammatory morphea and erythema migrans may appear to be similar at first, the lesions of erythema migrans are not indurated and often have a lighter-colored center. Most important, morphea should be differentiated from systemic sclerosis. This can be accomplished by appreciating digital sclerosis, Raynaud’s phenomenon, and internal organ involvement in the latter.
Ultrapotent topical steroids may reduce the inflammation of superficial morphea, and injection of triamcinolone into the active margins of morphea may halt progression. Other topical therapies that have been successful in the treatment of limited superficial inflammatory lesions include calcipotriene (Dovonex, Sorilux) and tacrolimus (Prograf).10 It should be noted that these are off-label uses of the medications.
Phototherapy with bath psoralen plus UVA or UVA1 therapy seems promising and has been shown to improve widespread deep morphea in approximately two-thirds of patients.10,11 Narrowband UVB may be appropriate for widespread superficial dermal plaques.10 For rapidly progressing disease, some have advocated weekly methotrexate (Rheumatrex, Trexall) combined with pulsed, high-dose corticosteroids.10,12
Other systemic therapies with limited evidence include treatment with penicillin and vitamin A derivatives. Physical therapy may be needed to prevent impaired mobility, and reconstructive surgery can help to alleviate persistent contractures.
Plaque-type morphea is a relatively harmless disease that usually progresses over the course of three to five years and then regresses slowly over a period of years. Some patients may develop disfigurement, contractures, or growth retardation depending on the affected area. Prompt treatment can help to avoid these complications.
In this case, a punch biopsy revealed inflammatory morphea. Therapeutic options were discussed, and the patient declined phototherapy or systemic treatment. Occluded tacrolimus 0.1% ointment b.i.d. was administered, and the lesions showed minimal improvement at a three-month follow-up exam.
Kerri Robbins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
- Bacon RM, Kugeler KJ, Mead PS; Centers for Disease Control and Prevention (CDC). Surveillance for Lyme disease—United States, 1992-2006. MMWR Surveill Summ. 2008;57:1-9. Available at www.cdc.gov/mmwr/preview/mmwrhtml/ss5710a1.htm.
- Tijsse-Klasen E, Jacobs JJ, Swart A, et al. Small risk of developing symptomatic tick-borne diseases following a tick bite in the Netherlands. Parasit Vectors. 2011;4:17. Available at www.ncbi.nlm.nih.gov/pmc/articles/pmid/21310036/.
- de Mik EL, van Pelt W, Docters-van Leeuwen BD, et al. The geographical distribution of tick bites and erythema migrans in general practice in the Netherlands. Int J Epidemiol. 1997;26:451-457. Available at ije.oxfordjournals.org/content/26/2/451.long.
- Wormser GP. Clinical practice. Early Lyme disease. N Engl J Med. 2006;354:2794-2801.
- Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345:79-84. Available at www.nejm.org/doi/full/10.1056/NEJM200107123450201.
- Peterson LS, Nelson AM, Su WP, et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993. J Rheumatol. 1997;24:73-80.
- Aberer E, Neumann R, Lubec G. Acrodermatitis chronica atrophicans in association with lichen sclerosus et atrophicans: tubulo-interstitial nephritis and urinary excretion of spirochete-like organisms. Acta Derm Venereol. 1987;67:62-65.
- Aberer E, Klade H, Stanek G, Gebhart W. Borrelia burgdorferi and different types of morphea. Dermatologica. 1991;182:145-154.
- Weide B, Schittek B, Klyscz T, et al. Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction. Br J Dermatol. 2000;143:780-785.
- Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol. 2011;65:925-941.
- Ghoreschi K, Röcken M. Phototherapy of sclerosing skin diseases. Dermatology. 2002;205:219-220.
- Uziel Y, Feldman BM, Krafchik BR, et al. Methotrexate and corticosteroid therapy for pediatric localized scleroderma. J Pediatr. 2000;136:91-95.
All electronic documents accessed May 15, 2013.