Are You Confident of the Diagnosis?
Considered to be a rare clinical variant of localized scleroderma or morphea, the characteristic lesions in atrophoderma of Pasini and Pierini (APP) consist of atrophic lesions or depressions rather than indurated plaques with lilac border. APP typically affects young adults, women outnumbering men, with no associated antecedent history of illness.
The lesions are usually asymptomatic, though some patient may report sensation of warmth or tingling. The skin findings consist of hyperpigmented or bluish patches and depressions on the trunk, particularly the back (Figure 1), and extremities. Face, hands, and feet are typically spared. Zosteriform and linear distribution have been described.
Characteristic findings on physical examination
Patients usually present with multiple lesions that range from subtle patches with minimal atrophy to obviously depressed lesions. The size of the lesions ranges from a few centimeters to greater than 15 cm. The depressed lesions may have a sharp drop off at the border (“cliff drop”) or a slope with gradual descent. The depressed areas are relatively smooth and flat, lacking significant surface irregularity (Figure 2). On palpation, a subtle induration may be appreciated in some lesions, but for the most part, they feel normal in texture. In some patients, lesions indistinguishable from classic lesions of morphea may be present concomitantly.
Expected results of diagnostic studies
The histopathologic findings in APP vary depending on the stage at which the lesion is biopsied. They are usually confined to the upper half of the reticular dermis, and thus referred to as superficial morphea by some. When early, non depressed, inflamed lesions are biopsied, there is a superficial perivascular and interstitial infiltrate of lymphocytes and plasma-cells with a subtle thickening of the collagen bundles (Figure 3) marked by subtle decrease in spaces between them. Homogenization of collagen in the papillary dermis may be observed, if involved.
If a depressed lesion is biopsied, differentiating from normal skin may prove challenging without a reference biopsy of normal skin because this is a pauci-inflammatory stage with subtle alteration of the collagen bundles, namely subtle thinned collagen bundles that manifest as increased spaces between them. Since these histopathologic changes are also observed in burned-out stage of classic morphea, some authors consider APP as burned-out morphea.
Although there are reports of altered elastic fibers in APP, the larger case series have not confirmed the findings. The diagnosis can be made with confidence based on the clinical findings alone. A biopsy may be performed to confirm the diagnosis and exclude other entities. As there are no confirmatory tests, no panel of serologic tests are recommended in the diagnosis of APP. However, serologic test for Lyme disease should be considered because therapeutic benefit has been observed in some of those patients with positive titers who were treated with antibiotics.
Other clinical entities with depressed lesions or atrophoderma include anetoderma, long-standing lupus profundus, eosinophilic fasciitis, lipodystrophy, and atrophoderma of Moulin. Except for atrophoderma of Moulin, these entities can be readily differentiated based on the history, clinical, and histopathologic findings.
In anetoderma, the lesions have a soft crinkly feel due to the significant alteration in the elastic fibers. The pathologic changes in lupus profundus, eosinophilic fasciitis, and lipodystrophy are found in the subcutis in contrast to APP. Atrophoderma of Moulin is characterized by hyperpigmented depressed lesions very similar to APP, but the distribution of the lesions follow the lines of Blaschko. Indeed, atrophoderma of Moulin may represent APP following the lines of Blashko.
Who is at Risk for Developing this Disease?
The condition has been reported in all age groups, but more frequently in young adult women in their 20s and 30s. The actual incidence of the disease is not known. Several of the larger observational studies have come out of Europe indicating that the disease may be more common in Europeans, but this may represent a publication bias. The disease has been rarely described in Asians and African Americans. There are no known risk factors that predispose individuals to develop APP.
What is the Cause of the Disease?
The cause of APP is unknown. In Europe, at least in one study, a small percentage of patients with APP have antibodies to Borrelia burgdorferi but the causative link has not been established and there exists no formal recommendation on testing for B burgdorferi antibodies in patients with APP.
Being a variant of morphea, APP is likely to share a common pathogenetic pathway as classic morphea. Similar to classic morphea, the clinical phenotype in APP represents a combination of defect in collagen metabolism in which there is alteration in collagen production and degradation. Although there is alteration in collagen metabolism, fibrocytes are not increased at any stage. The mononuclear cells observed in the inflammatory stage of APP are believed to be the mediators of fibrogenesis but the exact mechanism has not been elucidated.
Systemic Implications and Complications
APP is a skin-limited disease with no known systemic complications.
There is no effective treatment for APP. Since APP is considered a variant of morphea, patients have a theoretical risk of benefit with therapies that have been recommended for morphea. Anecdotal and cases series reports of specific therapies that have appeared in the literature include hydroxychloroquine400mg daily for a year , Q-switched Alexandrite laser, and oral antibiotics. Oral penicillin 2 million IU per day or tetracycline 500mg three times per day for two to three weeks have been reported to be successful.
An alternative to the reported antibiotic regimen is the standard Lyme disease antibiotic regimen for those patients with antibodies to B burgdorferi: amoxicillin 500mg three times daily or doxycycline 100mg twice daily for 3 weeks.
Optimal Therapeutic Approach for this Disease
Although the effectiveness of antibiotics has not been well studied, lacking any randomized clinical trials, oral penicillin 2 million IU per day or tetracycline 500mg three times per day may be administered to those patients with antibodies to Borrelia burgdorferi empirically.
Topical or short-course systemic corticosteroids may be tried in the early stage of the disease if an inflammatory stage is confirmed by biopsy.
The dosages of systemic corticosteroid may range from 0.5 to 1 mg/kg for a duration of several weeks to a few months with a subsequent taper.
Patients may be distraught about the appearance of the lesions, especially the hyperpigmentation. Laser therapy, namely the Q-switched Alexandrite laser, may be a reasonable approach for a limited number of hyperpigmented lesions.
Patients should be reassured that APP is a skin-limited disease with no systemic complications. The decision to treat should be based on realistic expectations of the patient as well as the understanding that any therapies for APP are not rooted in hard science.
Unusual Clinical Scenarios to Consider in Patient Management
Rarely, lesions of lichen sclerosis have appeared within lesions of APP, suggesting a common pathogenesis.
What is the Evidence?
Canizares, O, Sachs, PM, Jaimovich, L, Torres, VM. “Idiopathic atrophoderma of Pasini and Pierini”. Arch Derm. vol. 77. 1958. pp. 42-58. (This case series chronicles five patients with APP along with a review of the cases described previously, including those cases reported by Pasini and Pierini.)
Berman, A, Berman, GD, Winkelmann, RK. “Atrophoderma (Pasini-Pierini). Findings on direct immunofluorescent, monoclonal antibody, and ultrastructural studies”. Int J Dermatol. vol. 27. 1988. pp. 487-90. (This is a detailed case report that highlights clinical and histopathologic features including the inflammatory nature of APP.)
Buechner, SA, Rufli, T. “Atrophoderma of Pasini and Pierini. Clinical and histopathologic findings and antibodies to Borrelia burgdorferi in thirty-four patients”. J Am Acad Dermatol. vol. 30. 1994. pp. 441-6. (This is an observational European study, which highlights the association with B burgdorferi and treatment outcome with oral antibiotics. The numbers are small (n=34), but in 36% (10/26) of the patients who were tested had antibodies to B burgdorferi. Twenty of the 25 patients who were treated with oral antibiotics said to have some therapeutic benefit.)
Wakelin, SH, James, MP. “Zosteriform atrophoderma of Pasini and Pierini”. Clin Exp Dermatol. vol. 20. 1995. pp. 244-6. (This is a case report that highlights unilateral presentation.)
Kencka, D, Blaszczyk, M, Jablonska, S. “Atrophoderma Pasini-Pierini is a primary atrophic abortive morphea”. Dermatol. vol. 190. 1995. pp. 203-6. (This is the largest series of patients (n=139) from Europe, but the analyses and details of the cases are limited. The disease was more frequent in women, self-limiting in that it did not require treatment. Because none of the cases developed full blown morphea, the authors considers APP as an “abortive” form of morphea.
Arpey, CJ, Patel, DS, Stone, MS, Qiang-Shao, J, Moore, KC. “Treatment of atrophoderma of Pasini and Pierini- associated hyperpigmentation with the Q-switched alexandrite laser: a clinical, histologic, and ultrastructural appraisal”. Lasers Surg Med. vol. 27. 2000. pp. 206-12. (This case report highlights the limited efficacy of Q-switched Alexandrite laser in the treatment of hyperpigmentation in APP. A complete response was not observed, but clinical improvement in the hyperpigmentation was observed after three treatments.)
Jablonska, S, Blaszczyk, M. “Is superficial morphea synonymous with atrophoderma Pasini-Pierini?”. J Amer Acad Dermatol. vol. 50. 2004. pp. 979-80. (This is an opinion piece that asks the readers to abandon the designation APP and replace it with superficial morphea. The readers need to decide whether the argument is convincing.)
Carter, JD, Valeriano, J, Vasey, FB. “Hydroxychloroquine as a treatment for atrophoderma of Pasini and Pierini”. Int J Dermatol. vol. 45. 2006. pp. 1255-6. (This case report highlights the successful treatment with hydroxychloroquine in a patient who had APP for more than 17 years. The lesions resolved completely after 1 year of therapy with 400mg of hydroxychloroquine a day.
Saleh, Z, Abbas, O, Dahdah, MJ, Kibbi, AG, Zaynoun, S, Ghosn, S. “Atrophoderma of Pasini and Pierini: a clinical and histopathological study”. J Cutan Pathol. vol. 35. 2008. pp. 1108-14. (This case series adds another 16 cases of APP to the literature. In contrast to previously reported cases, the authors note that APP lesions may be hypopigmented and elastic fibers may be diminished or fragmented.)
Fett, N, Werth, VP. “Update on morphea part I. Epidemiology, clinical presentation, and pathogenesis”. J Am Acad Dermatol. vol. 64. 2011. pp. 217-28. (This is a comprehensive review of morphea that highlights the different classifications of morphea that include APP. The topics of discussion are relevant to APP being a clinical variation of morphea.)
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