Acrodermatitis Chronica Atrophicans Workup

Updated: Mar 26, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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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:

  • Careful evaluation of the history, including epidemiologic data and symptoms of early and late infection

  • A detailed physical examination

  • Specific serologic tests results and the histopathologic picture of skin biopsy specimens

Sometimes, if the clinical presentation is compatible and a high level of serum B burgdorferi IgG antibodies is detected, a presumptive diagnosis is rendered, ideally confirmed histologically. [22]

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.

Molecular methods to detect borrelial DNA hold promise for the future. [23]


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. [10] In the authors’ series of 9 patients, all had results that were positive for IgG, and 5 had results that were positive for IgM. [10]

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. [24, 25] 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. [26] . 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. [27]

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).

Biopsy specimen from the wrist of the patient show 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 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.

A higher magnification of the same biopsy specimen 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. Sometimes, one sees prominent granuloma annulare‒like or lichenoid changes. [18]

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. [28]

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.