Acrodermatitis Chronica Atrophicans

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Background

Acrodermatitis chronica atrophicans (ACA) is the third or late stage of European Lyme borreliosis.[1, 2] This unusual progressive fibrosing skin process is caused by an ongoing active infection with Borrelia afzelii. First delineated in 1883,[3] it was described in 1902 as a tissue paper–like cutaneous atrophy.[4]

ACA is evident on the extremities, particularly on the extensor surfaces. It begins with an inflammatory stage characterized by bluish red discoloration and cutaneous swelling and concludes 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.

The choice of treatment for ACA depends on the coexistence of other signs or symptoms of Lyme borreliosis. Appropriate consultations (ie, a neurologist, ophthalmologist, rheumatologist, or cardiologist) should be sought if extracutaneous signs and symptoms are present. ACA patients without concurrent extracutaneous disease do not require hospitalization.

Pathophysiology and Etiology

B afzelii is the predominant etiologic agent of ACA but may not be the sole cause. Borrelia garinii, another genospecies of the Borrelia burgdorferi sensu lato (“in the broad sense”) complex, has also been detected in this setting.

ACA is the only form of Lyme borreliosis 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 the following factors:

Lack of protective antibodies, with a narrow antibody spectrum and a weak cellular response characterized by downregulation of major histocompatibility system (MHC) class II molecules on Langerhans cells, has been observed in patients with Lyme borreliosis.

A restricted pattern of cytokine expression in ACA, including 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 also has not been clarified. Perhaps periarticular regions are favored sites because of reduced acral skin temperatures or reduced oxygen pressure.

Lack of adequate or appropriate treatment of early Lyme borreliosis facilitates the development of ACA.

Epidemiology

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

United States statistics

Ixodes scapularis, Ixodes pacificus, and 4 other tick species distributed in North America transmit B burgdorferi sensu stricto (“in the strict sense”), causing erythema migrans and Lyme borreliosis arthritis.

Despite a high incidence of Lyme borreliosis in the United States (ranging from 95 cases per 100,000 population in Connecticut to 1250 cases per 100,000 population in Nantucket County, MA [1996 data]), ACA is not seen in the United States, except in a few European immigrants.[5]

International statistics

The tick vectors of B afzelii, the main etiologic agent of ACA (and erythema migrans), are Ixodes ricinus, Ixodes hexagonus, and Ixodes persulcatus, which are 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 erythema migrans and neurologic symptoms of Lyme borreliosis.

In Europe, Lyme borreliosis with all its dermatologic manifestations occurs in almost all countries, predominantly in the central part of the continent. The annual incidence ranges from 16 cases per 100,000 population in France to 120 cases per 100,000 population in northeastern Poland and Slovenia and to 130 cases per 100,000 population in Austria (1995 data).[6]

The overall prevalence of ACA in all European patients with Lyme borreliosis is about 1-10%, depending on the region of the population sampled. Among the group of patients with skin manifestations of Lyme borreliosis observed in Vienna, the ratio of erythema migrans cases to ACA cases and to Borrelia lymphocytoma (BL) cases was 30:3:1. In the authors’ as-yet-unpublished studies (involving a group of patients with Lyme borreliosis in northeastern Poland), this ratio is 170:5:1.

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

A Bulgarian survey found that both BL and ACA were rare (0.3%).[7]

Of over 700 patients from an endemic region of northern Italy, erythema migrans was noted in more than half, with 7 having lymphadenosis benigna cutis and 18 ACA.[8]

Age-related demographics

ACA can occur in any age group but it is most common in adults, mainly those in their 40s or 50s. The youngest of the authors’ patients was 26 years of age; the oldest was 73 years.[9] 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.[10]

Sex-related demographics

More than two thirds of patients with ACA are women. Of the authors’ 19 patients, only 5 were men.[9]

Race-related demographics

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

Prognosis

The course of ACA is prolonged and may extend for as long as several years. It leads to extensive flaccid atrophy of the skin and, in some patients, to limitation of upper and lower limb joint mobility. Chronic, difficult-to-treat ulcerations of atrophic skin may develop after minor trauma. Bacterial superinfections may be seen.

The general status of patients with ACA remains good, though they may experience neurologic or rheumatologic signs and symptoms. As a rule, the outcome of treatment is good if the acute inflammatory stage of ACA is treated adequately. The therapeutic outcome is difficult to assess in patients with the chronic atrophic phase, in which many changes are only partially reversible.

Although ACA rarely occurs in childhood, its prognosis in pediatric patients is uncertain. For this reason, it should be treated as early as possible to prevent irreversible cutaneous damage.[11]

Rarely, a B-cell lymphoma may develop in these patients, as may a basal cell carcinoma or squamous cell carcinoma.[12] A metastatic cutaneous squamous cell carcinoma was described in a patient with long-standing ACA. On the whole, however, malignant degeneration has been quite uncommon; accordingly, ACA should not be considered a precancerous disorder.

Patient Education

Patients and their families should receive information about how to lower the risk of acquiring ACA. Persons residing in endemic areas should examine their bodies for ticks every 12 hours and should expeditiously remove any attached ticks. To discourage ticks from accessing exposed skin, they should use personal protection (eg, light-colored clothing to facilitate tick visualization) and tuck their pants cuffs into socks.

For patient education resources, see the Bacterial and Viral Infections Center and Bites and Stings Center, as well as Lyme disease and Ticks.

History

Because of the late onset of acrodermatitis chronica atrophicans (ACA), patients rarely remember a tick bite. Instead, they recall having been in the woods or grassy areas a few months or years previously, especially in a geographically endemic region.

About 20% of patients report a history of erythema migrans. ACA can develop directly from EM or can arise after 6-36 months, often involving the same region of the body. Sometimes, the disease may be preceded by a latent phase (lasting up to several years) or by other manifestations of Lyme borreliosis; the latter can also develop simultaneously.

Commonly, the patient notices localized cutaneous swelling on the distal extremity or on a single digit; sometimes, he or she discovers that one foot is larger than the other when buying shoes. ACA is most often unilateral, although bilateral ACA is also common.

Progressive allodynia (exaggerated reaction to pain) is a characteristic symptom and thus may be a clue to the diagnosis of ACA. Patients commonly report spontaneous acral pain and paresthesia or dysesthesia or cognitive dysfunction.

ACA starts with an inflammatory phase, characterized by multiple soft, erythematous, slowly enlarging cutaneous swellings or flat infiltrations of various sizes or by diffuse bluish red discoloration and edema of the skin. As noted, it usually appears on the distal part of at least one extremity, predominantly on the extensor surfaces of the bony prominences (see the image below).


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The typical inflammatory phase patches are seen on the right hand bone prominences.

Common sites of ACA are the foot, the lower leg or the hand, the forearm, and the olecranon area (see the image below); proximal locations on the upper arm and the shoulder or the thigh and the buttock may be seen but are uncommon. Sometimes, the erythema is slight and swelling may dominate, or the signs may be very subtle and go unrecognized by the patient or the physician. Lymphadenopathy may be noticed.


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The most common localization of the skin lesions in 12 patients with acrodermatitis chronica atrophicans (ACA). The number of ACA lesions in the parti....

For many months or years, only a single part of an extremity may be affected. With time, the skin lesions may extend on 1 extremity or may appear on additional extremities and also involve other parts of the body.

Fibrotic nodules (often multiple, localized linearly in the vicinity of joints) are typical. They can precede ACA or develop simultaneously with it. The most common sites of these nodules are the elbows and the knees.

ACA does not heal spontaneously; gradual conversion into its atrophic phase may occur over many years of infection. In this later phase, the skin becomes thin, atrophic, wrinkled, dry, and translucent. The hair is lost, and the numbers of sebaceous and sweat glands are decreased. Even minor trauma may produce large, slow-to-heal ulcerations of the affected skin.

About 5-10% of patients with ACA develop sclerodermalike plaques. Anetodermalike skin lesions can be seen concomitant with ACA.

Frequently, ACA is accompanied by peripheral neuropathy, musculoskeletal pains, and joint damage underneath the cutaneous plaques. Involvement of the small joints of the hands and the feet by the fibrotic reaction is often seen.

Physical Examination

Clinical recognition of ACA may be difficult, even in typical cases. A detailed history, including epidemiologic data, is helpful. Physicians should confirm the clinical diagnosis by means of histopathologic examination and serologic testing.

The early, inflammatory phase of acrodermatitis chronica atrophicans is marked by soft, painless, poorly demarcated, bluish red plaques that tend to coalesce or by diffuse erythema and edema localized on the distal extremities that spread proximally (see the images below).


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A 73-year-old female farmer with a cutaneous plaque on the sole of her right foot lasting for 6 months that, in the meantime, had extended onto the do....


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A 50-year-old male farmer was examined for cutaneous plaques on the dorsal side of his right hand lasting for 8 months that, in the meantime, had exte....


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A 68-year-old woman with a history of untreated erythema migrans on her left thigh 2 years previously. Ten months later, the plaque extended over the ....

In the authors’ experience, not only the distal extremities but also the proximal parts, the trunk, and the face may be involved in the early stage of ACA. Others have also observed skin-colored facial edema as an initial manifestation of ACA (see the images below).[13] Skin changes are often associated with regional or generalized lymphadenopathy.


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A 69-year-old woman. The initial lesion developed on the dorsal side of her left hand 2 years previously and extended onto her left forearm and arm. A....


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The inflammatory phase of acrodermatitis chronica atrophicans can be seen with rosacea lesions on the cheek, the forehead, and the nose.

The later, atrophic phase of ACA is more characteristic clinically (see the images below). The affected skin exhibits the following:

Because of the loss of subcutaneous fat, the skin vessels become prominent. Atrophy of the epidermis and lack of hairs, sebaceous glands, and often sweat glands make the skin poorly protected and vulnerable. Large ulcerations can be observed, and malignant lesions may also occur. The atrophic poikilodermic changes are often bilateral and most noticeable over the knees, the elbows, and the dorsal surfaces of the hands and the feet. They may also involve the trunk (particularly the chest) and the face. Note the image below.


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A 48-year-old woman with a history of frequent tick bites and an initial inflammatory skin lesion on the left medial part of her ankle 2 years previou....

Sclerodermalike changes may appear in both the inflammatory phase and the atrophic phase of ACA. These changes are usually limited to the legs and the feet, but they occasionally occur on the trunk. The lesions, similar to morphea and lichen sclerosus and atrophicus, may appear in regions where no ACA is present.

Single or multiple fibrotic nodules or bands may be seen on the extensor surfaces of the elbows and the knees or adjacent to other joints (see the image below). They are generally firm; bluish red, yellowish, or skin-colored; and 0.5 to 3 cm in diameter.


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Fibrotic nodules on the left elbow.

ACA has been described in association with localized amyloidosis, eczema, psoriasis, lupus erythematosus, leprosy, and Hodgkin disease; however, these associations may be coincidental. One of the authors’ patients with histologically and serologically confirmed ACA was a 68-year-old woman first seen with prominent livedo racemosa on the leg where typical ACA inflammatory-phase patches developed.[9] Others observed the same phenomenon; thus, this may be more than a chance linkage.

Detailed clinical and neurophysiologic examinations in patients with ACA-associated polyneuropathy often show a sensory polyneuropathy. Neuropathy symptoms (typically pain, paresthesia or both) are evident in one half of patients with ACA. One of the authors’ patients had paresis of the brachial plexus.[9] Marked abnormality of the vibratory threshold is a common finding.

Patients with localized or asymmetric neuropathy seem to have changes more often found in the extremities with, rather than without, visible acrodermatitis chronica atrophicans lesions. Abnormalities in cerebrospinal fluid seldom have been found in patients with acrodermatitis chronica atrophicans.

ACA can produce deformities of the fingers and the toes if it is not treated promptly. Persistent reducible deformities of the fingers may be consistent with Jaccoud arthropathy.

Approach Considerations

Genetic profiles of strains of B burgdorferi sensu lato derived from patients with acrodermatitis chronica atrophicans (ACA) often show the highly conserved MLa1 pattern characteristic of B afzelii; however, they may demonstrate the large restriction fragment patterns typical of B garinii.

The diagnosis of ACA should be based on the following:

A negative history of exposure to ticks should not exclude the diagnosis. B afzelii can be identified in skin lesions by means of polymerase chain reaction (PCR) testing, but both cultures and direct spirochetal stains are usually negative.

Laboratory Studies

Laboratory evidence of infection, obtained by demonstrating specific antibodies with a 2-test approach that involves initial screening with enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay (IFA) and subsequent confirmation of positive and equivocal results with Western blot, is essential for diagnosis of Lyme borreliosis. All patients with ACA are seropositive for immunoglobulin G (IgG), and some are also positive for immunoglobulin M (IgM) antiborrelial antibodies.

Either IFA or ELISA can yield false-positive results as a consequence of cross-reactivity with Treponema pallidum, saprophytic Treponema and other spirochetal agents (ie, Leptospira species), and rheumatoid factor. False-positive results may also occur in patients with infectious mononucleosis and other disorders with activated B cells.

In regions where there is a high incidence of syphilis (eg, Central Europe, Eastern Europe, Central Asia), T pallidum infection should be excluded in every case of B burgdorferi seropositivity by using the T pallidum hemagglutination assay (TPHA). B burgdorferi infection should also be ruled out in cases of false-positive serologic tests results for syphilis. ELISA using sonicated or purified or recombinant antigens of B burgdorferi seems to be more specific than IFA using cultured Borrelia and serum preexposed to nonpathogenic Treponema phagedenis.

Immunoblotting with various B burgdorferi antigens is used as a confirmatory test for Lyme borreliosis. The authors found that the immunoblot technique with B afzelii flagellar antigen (41 kd) is useful in the diagnosis of ACA.[9] In the authors’ series of 9 patients, all had results that were positive for IgG, and 5 had results that were positive for IgM.[9]

In the authors’ opinion, the strategy for serologic diagnosis of ACA (as in cases of late syphilis) should include assessment of quantitative serologic test results (ie, IFA results) because a high titer of antibodies, even in persons without clinical signs and symptoms of neuroborreliosis, may point to central nervous system (CNS) involvement and indicate the need to evaluate the cerebrospinal fluid (CSF) for intrathecal production of antiborrelial antibodies.

Because ACA is often confused with vascular conditions, serologic proof of the diagnosis and histologic verification are considered obligatory.[14] PCR testing for Borrelia -specific DNA (rather than culture of the spirochete) is sometimes a necessary adjunctive measure. Borrelia has been only rarely isolated from the blood culture in these patients. For example, in one study, the organism was isolated from blood in only 3 (1.5%) of 200 ACA patients.[15] . PCR for B burgdorferisensu lato with formalin-fixed, paraffin-embedded biopsies was performed in a routine dermatopathology laboratory, with genotyping of subspecies or strains being successful in 10 of 10 patients with ACA in one German study.[16]

Radiologic findings in patients with ACA may show subluxation of the toe joint and periostitis of the bones of the lower limb.

Sural nerve biopsy may demonstrate a mainly axonal neuropathy. CSF testing shows mononuclear pleocytosis and intrathecal production of specific antibodies when the CNS is involved.

Histologic Findings

The most important histologic findings in ACA are the presence of telangiectasias and the presence of cellular infiltrates of lymphocytes with admixed plasma cells in the absence of any other explanation for the plasma cells (eg, syphilis or myeloma). Although these changes are not diagnostic, they are highly suggestive (see the images below).


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Biopsy specimen from the wrist of the patient shown in Image 4. The epidermis is slightly flattened. A zone of normal connective tissue can be seen be....


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A higher magnification. Telangiectatic vessels are surrounded by a cellular infiltrate in the upper dermis.

In its early inflammatory stage, ACA shows a dense, patchy perivascular and periappendigeal dermal infiltrate of lymphocytes, histiocytes, and plasma cells (see the image below). Collagen bundles become swollen and homogeneous and are split by mucinous deposition.


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A higher magnification of the same biopsy specimen. Note the patchy cell infiltrate around the large vessels in the deep dermis.

In its atrophic stage, ACA demonstrates striking epidermal atrophy, a normal zone just below the epidermis, dilated blood vessels, and a lymphocytic–plasma cell infiltrate within the upper dermis. Plasma cell–rich infiltrates within a sclerotic dermis should suggest the possibility of ACA. Neural lymphocytic infiltration may be evident. Leukocytoclastic vasculitis or vessel occlusion may be seen in some cases. The subcutis is involved in a large percentage of patients.

Pseudolymphomatous infiltrates with both a T-cell and, less frequently, a B-cell pattern may be evident within ACA, requiring distinction from a cutaneous lymphoma.[17]

Warthin-Starry stains may show spirochetes in some cutaneous biopsy specimens, though this often is not the case. Immunohistochemical studies show few B cells despite a substantial number of plasma cells.

Approach Considerations

The choice of treatment for acrodermatitis chronica atrophicans (ACA) depends on the coexistence of other signs or symptoms of Lyme borreliosis. One should also take into account the results of serologic tests. If not treated early, ACA can be associated with joint manifestations and persistent finger deformities.

Appropriate consultations (ie, neurologist, ophthalmologist, rheumatologist, cardiologist) should be sought if extracutaneous signs and symptoms are present. ACA patients without concurrent extracutaneous disease do not require hospitalization.

The US Food and Drug Administration (FDA) approved a vaccine against Lyme borreliosis for distribution in the United States in January 1999, but it is not currently in general use. At present, for European countries, a recombined vaccine is being prepared from the surface lipoprotein A (OspA) made from prevalent strains of B afzelii and B garinii.

Pharmacologic Therapy

If extracutaneous Lyme borreliosis signs are absent and the level of specific antibodies is low, the authors usually recommend oral doxycycline or oral amoxicillin administered over a period of 3 weeks.

If organic or systemic physical or laboratory signs of Lyme borreliosis are present or if the antibody titer is high, appropriate treatment should be initiated, typically with ceftriaxone or cefotaxime or aqueous penicillin G given intravenously (IV) for 21-28 days.

The possibility of another concurrent infection (eg, babesiosis, ehrlichiosis, or tick-borne encephalitis) must be kept in mind. About 10% of patients with Lyme disease in southern New England are coinfected with babesiosis, and about the same percentage in parts of the Midwestern United States have human granulocytic ehrlichiosis (HGE). Unlike ehrlichiosis, which is usually a short-lived infection, babesiosis can be persistent and may coexist with ACA.

Patients in the early phase of ACA should be assured that resolution of symptoms may occur gradually over a period of several weeks or months after treatment (see the images below); patients treated in the atrophic phase should be informed that although disease progression can be stopped, the symptoms may be only partially reversible.


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After 30 days of treatment with ceftriaxone.


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The same patient after treatment.

Long-Term Monitoring

Initially, follow-up care should be performed every 3-6 months; later, it may be performed once a year. Physical examination for signs and symptoms of cutaneous and extracutaneous manifestations of Lyme borreliosis is important. In most ACA patients who have received antibiotic therapy, quantitative serologic tests show IgG antibody titers that either do not change or decline only to a certain extent.

Despite the persistence of IgG antibody response in late Lyme borreliosis (serologic scar), similar to that observed in syphilis cases, the authors do serologic follow-up testing according to the recommendation for late syphilis. A sudden increase in antibody titer can point to the activation of infection and precede a clinical recurrence of the disease.

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. Various antibiotics are used to treat acrodermatitis chronica atrophicans (ACA).

Amoxicillin (Moxatag)

Clinical Context:  Amoxicillin is bactericidal against Borrelia species. It is a semisynthetic penicillin of the aminopenicillin group that demonstrates a wide spectrum of bactericidal activity related to gram-positive and gram-negative bacteria. Its mechanism of action involves inhibition of

Doxycycline (Vibramycin, Adoxa, Doryx, Monodox)

Clinical Context:  Doxycycline is a tetracycline antibiotic that inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It is used for its antibacterial and anti-inflammatory effect and may be considered when there is concern about possible coexistent infection.

Ceftriaxone (Rocephin)

Clinical Context:  Ceftriaxone is bactericidal against Borrelia species. It is a third-generation cephalosporin with broad-spectrum gram-negative activity. Ceftriaxone has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Cefotaxime (Claforan)

Clinical Context:  Cefotaxime is a third-generation semisynthetic cephalosporin with broad-spectrum bactericidal activity against gram-negative bacteria and Staphylococcus and Streptococcus species. It is resistant to beta-lactamases. Its mechanism of action is related to inhibition of bacteria cell wall synthesis.

Penicillin G (Pfizerpen)

Clinical Context:  Penicillin G is a beta-lactam antibiotic. Its mechanism of action is related to inhibition of bacterial cell wall synthesis in the growth phase as a result of penicillin and bacterial transpeptidase binding.

Class Summary

Empiric antimicrobial therapy for ACA must be comprehensive and should cover all pathogens likely to be present in the context of this clinical setting.

Author

Bozena Chodynicka, MD, Head, Professor, Department of Dermatology and Venereology, Medical University of Bialystok, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Iwona Flisiak, MD, Assistant Professor, Department of Dermatology and Venereology,Medical University of Bialystok, Poland

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Ackerman Academy of Dermatopathology, New York

Disclosure: Nothing to disclose.

Additional Contributors

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Peter Fritsch, MD Chair, Department of Dermatology and Venereology, University of Innsbruck, Austria

Peter Fritsch, MD is a member of the following medical societies: American Dermatological Association, International Society of Pediatric Dermatology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

References

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The typical inflammatory phase patches are seen on the right hand bone prominences.

The most common localization of the skin lesions in 12 patients with acrodermatitis chronica atrophicans (ACA). The number of ACA lesions in the particular body region is shown.

A 73-year-old female farmer with a cutaneous plaque on the sole of her right foot lasting for 6 months that, in the meantime, had extended onto the dorsum of her foot, her right leg, and the lower part of her right thigh. Infection of Borrelia burgdorferi was diagnosed with enzyme-linked immunosorbent assay, and acrodermatitis chronica atrophicans was confirmed histologically.

A 50-year-old male farmer was examined for cutaneous plaques on the dorsal side of his right hand lasting for 8 months that, in the meantime, had extended onto his right forearm and arm and had also developed on his right thigh. The patient complained of muscular weakness related to his right upper limb and periodic arthralgia. The neurologic examination demonstrated signs of right brachial plexus damage, confirmed by electromyography. Borrelia burgdorferi infection was diagnosed with enzyme-linked immunosorbent assay, indirect immunofluorescence assay (titer: 1:1,024), and Western blot. Histologic examination confirmed the diagnosis of acrodermatitis chronica atrophicans.

A 68-year-old woman with a history of untreated erythema migrans on her left thigh 2 years previously. Ten months later, the plaque extended over the skin of her left buttock and became bluish with signs of livedo racemosa. Her forearms and breast were also involved. Borrelia burgdorferi infection was diagnosed with indirect immunofluorescence assay (1:4,096) and Western blot. Acrodermatitis chronica atrophicans was confirmed histologically. Because of intrathecal production of specific antibodies, diagnosis of asymptomatic neuroborreliosis was established.

A 69-year-old woman. The initial lesion developed on the dorsal side of her left hand 2 years previously and extended onto her left forearm and arm. A new erythematous lesion developed 2 months before on her right cheek beside the rosacea signs. Acrodermatitis chronica atrophicans was confirmed in the biopsy specimen taken from the skin of the forearm, and Borrelia burgdorferi infection was diagnosed with indirect immunofluorescence assay (1:2,048). The atrophic phase of acrodermatitis chronica atrophicans is visible on the hand, and the inflammatory phase is visible on the cheek.

The inflammatory phase of acrodermatitis chronica atrophicans can be seen with rosacea lesions on the cheek, the forehead, and the nose.

Atrophic phase of acrodermatitis chronica atrophicans of the right upper limb with induration of the forearm.

A widespread acrodermatitis chronica atrophicans atrophic plaque on the back.

The atrophic skin lesions and fibrotic nodules of the right upper limb.

A 48-year-old woman with a history of frequent tick bites and an initial inflammatory skin lesion on the left medial part of her ankle 2 years previously. The lesion extended onto the left leg and involved the knee. Fibrotic nodules developed in the medial part of the ankle and the knee. Moreover, she complained of balance disturbances and vertigo. Neurologic examination revealed the asymmetry of profound reflexes, bilateral lack of plantar reflexes with a tendency to the extensor plantar response (Babinski sign), ataxia, profound dysesthesia, and muscular atrophy of the left calf. Acrodermatitis chronica atrophicans was confirmed by histologic examination, and Borrelia burgdorferi infection was confirmed by a high specific antibody titer with indirect immunofluorescence assay (1:8,192); cerebrospinal fluid was not tested.

Fibrotic nodules on the left elbow.

Biopsy specimen from the wrist of the patient shown in Image 4. The epidermis is slightly flattened. A zone of normal connective tissue can be seen below the epidermis. A patchy infiltrate consisting of lymphocytes and plasma cells is seen throughout the dermis. Telangiectasias are evident in the upper and deeper parts of the dermis.

A higher magnification. Telangiectatic vessels are surrounded by a cellular infiltrate in the upper dermis.

A higher magnification of the same biopsy specimen. Note the patchy cell infiltrate around the large vessels in the deep dermis.

After 30 days of treatment with ceftriaxone.

The same patient after treatment.

The most common localization of the skin lesions in 12 patients with acrodermatitis chronica atrophicans (ACA). The number of ACA lesions in the particular body region is shown.

A 73-year-old female farmer with a cutaneous plaque on the sole of her right foot lasting for 6 months that, in the meantime, had extended onto the dorsum of her foot, her right leg, and the lower part of her right thigh. Infection of Borrelia burgdorferi was diagnosed with enzyme-linked immunosorbent assay, and acrodermatitis chronica atrophicans was confirmed histologically.

The external part of the right foot.

A 50-year-old male farmer was examined for cutaneous plaques on the dorsal side of his right hand lasting for 8 months that, in the meantime, had extended onto his right forearm and arm and had also developed on his right thigh. The patient complained of muscular weakness related to his right upper limb and periodic arthralgia. The neurologic examination demonstrated signs of right brachial plexus damage, confirmed by electromyography. Borrelia burgdorferi infection was diagnosed with enzyme-linked immunosorbent assay, indirect immunofluorescence assay (titer: 1:1,024), and Western blot. Histologic examination confirmed the diagnosis of acrodermatitis chronica atrophicans.

The typical inflammatory phase patches are seen on the right hand bone prominences.

A 68-year-old woman with a history of untreated erythema migrans on her left thigh 2 years previously. Ten months later, the plaque extended over the skin of her left buttock and became bluish with signs of livedo racemosa. Her forearms and breast were also involved. Borrelia burgdorferi infection was diagnosed with indirect immunofluorescence assay (1:4,096) and Western blot. Acrodermatitis chronica atrophicans was confirmed histologically. Because of intrathecal production of specific antibodies, diagnosis of asymptomatic neuroborreliosis was established.

After 30 days of treatment with ceftriaxone.

The livedo racemosa and acrodermatitis chronica atrophicans lesions on the left thigh and buttock before treatment.

The same patient after treatment.

A 69-year-old woman. The initial lesion developed on the dorsal side of her left hand 2 years previously and extended onto her left forearm and arm. A new erythematous lesion developed 2 months before on her right cheek beside the rosacea signs. Acrodermatitis chronica atrophicans was confirmed in the biopsy specimen taken from the skin of the forearm, and Borrelia burgdorferi infection was diagnosed with indirect immunofluorescence assay (1:2,048). The atrophic phase of acrodermatitis chronica atrophicans is visible on the hand, and the inflammatory phase is visible on the cheek.

The inflammatory phase of acrodermatitis chronica atrophicans can be seen with rosacea lesions on the cheek, the forehead, and the nose.

Fibrotic nodules on the left elbow.

A 48-year-old woman with a history of frequent tick bites and an initial inflammatory skin lesion on the left medial part of her ankle 2 years previously. The lesion extended onto the left leg and involved the knee. Fibrotic nodules developed in the medial part of the ankle and the knee. Moreover, she complained of balance disturbances and vertigo. Neurologic examination revealed the asymmetry of profound reflexes, bilateral lack of plantar reflexes with a tendency to the extensor plantar response (Babinski sign), ataxia, profound dysesthesia, and muscular atrophy of the left calf. Acrodermatitis chronica atrophicans was confirmed by histologic examination, and Borrelia burgdorferi infection was confirmed by a high specific antibody titer with indirect immunofluorescence assay (1:8,192); cerebrospinal fluid was not tested.

A 26-year-old female nurse recalled the onset of the disease on her right arm 4 years before. After 6 months, the plaques extended onto the right forearm and hand. The left arm and forearm were also involved 3 years previously. Induration of the skin of the right forearm was noted. Borrelia burgdorferi infection was diagnosed with indirect immunofluorescence assay (1:2,048) and confirmed by positive Western blot for both immunoglobulin M and immunoglobulin G antibodies.

Atrophic phase of acrodermatitis chronica atrophicans of the right upper limb with induration of the forearm.

A 68-year-old female jogger frequently exposed to ticks. Cutaneous plaques developed 4 years previously on her right lower limb and the right part of her trunk, including her breast and right upper limb. Typical extensive cigarette paper–like plaques, bluish or brownish red in color were evident. Fibrous nodules were found on her right elbow. Borrelia burgdorferi infection was confirmed with indirect immunofluorescence assay (1:1,024) and Western blot. Acrodermatitis chronica atrophicans was finally diagnosed by using histologic examinations.

A widespread acrodermatitis chronica atrophicans atrophic plaque on the back.

The atrophic skin lesions and fibrotic nodules of the right upper limb.

Biopsy specimen from the wrist of the patient shown in Image 4. The epidermis is slightly flattened. A zone of normal connective tissue can be seen below the epidermis. A patchy infiltrate consisting of lymphocytes and plasma cells is seen throughout the dermis. Telangiectasias are evident in the upper and deeper parts of the dermis.

A higher magnification. Telangiectatic vessels are surrounded by a cellular infiltrate in the upper dermis.

A higher magnification of the same biopsy specimen. Note the patchy cell infiltrate around the large vessels in the deep dermis.