2013 January-March; 1(1): 29–36. ISSN: 2282-4103
Published online 2013 April 5.

Atrophoderma following the lines of Blaschko: an interesting diagnostic dilemma. Linear Atrophoderma of Moulin, blaschkolinear Atrophoderma of Pasini and Pierini or linear morphea?

Annalisa Patrizi, Michela Venturi, Iria Neri, Massimiliano Pazzaglia, and Beatrice Passarini

Dermatology - Department of Specialised, Experimental and Diagnostic Medicine, University of Bologna, Bologna, Italy

Address for correspondence: Annalisa Patrizi, MD, Dermatology - Department of Specialised, Experimental and Diagnostic Medicine, S. Orsola - Malpighi Hospital, Via Massarenti, 1, 40138 Bologna, Italy, Phone: +39 051 6364847, Fax: +39 051347847, E-mail: annalisa.patrizi@unibo.it

Summary

Dermatoses that may present in a linear distribution and with quite similar histological findings include linear atrophoderma of Moulin (LAM), atrophoderma of Pasini and Pierini (APP) and linear morphea. We present a review of the literature and two new cases that could be diagnosed as LAM, one of which is the oldest one ever described while the other has an ususual bilateral localization. The distribution along Blaschko’s lines (BL) was a characteristic of LAM, but some cases have been later redefined as blaschkolinear APP or morphea following the BL. In fact, even though Moulin et al. described biopsy specimens with just a basal hyperpigmentation overlying an unaltered dermis, some published cases of LAM present different histological findings but have been classified under the same umbrella. Whether or not our patients represent a genuine form of LAM will depend on how willing we are to expand the definition of LAM. We suggest that the too subtle and overlapping histopathological findings of a single biopsy specimen could just reflect different stages of the spectrum of an evolving dermatosis. Thus, a long follow-up with repeated biopsies should be performed in order to reach the correct definitive diagnosis.

Keywords: linear atrophoderma of Moulin, atrophoderma of Pasini and Pierini, linear morphea, Blaschko’s lines

Introduction

Linear Atrophoderma of Moulin (LAM) is a rare skin condition and first described in 1992 by Moulin et al. (1) who reported 5 healthy young patients affected by unilateral, hyperpigmented, depressed plaques along BL on the trunk and extremities, without any evidence of long-term progression. Inflammation, induration or sclerosis did not precede the skin lesions (1, 2). The main histological finding was a basal hyperpigmentation, while the other epidermal layers and the dermis were normal, including normal-appearing collagen and elastic fibers (13). Thus, the clinical atrophy was initially linked to an alteration of the subcutaneous tissue, but a deep biopsy on both the affected and controlateral sides was originally not performed.

Moulin et al. (1) suggested the term “blaschkose”, in opposition to “blaschkitis” with an inflammatory and acquired significance. Later, this skin desease was named “LAM” by Baumman et al. (4), who classified this disease as belonging to the group of acquired linear dermatoses following BL and thought LAM as a variant of progressive atrophoderma of Pasini and Pierini (APP). In the literature, the clinical and histopathological criteria for the diagnosis of LAM have been expanded in the last years, and cases with different clinical and histological features have been classified as LAM (3, 5).

Report of cases

Case 1
A 38-year-old man referred to us for hyperpigmented linear skin lesions. These slightly atrophic and brownish macules localised along the BL involved his chest, the axillas and shoulders, running along his right and left arms, and were also present on both buttocks and the right leg (Figure 1). They measured 3 cm in diameter and coalesced to form “S” shaped bands of up to 8 cm in length on the arms. On the right shoulder the biggest lesion was 8 cm X 9 cm, while on the right leg the band was 2 cm wide and 3 cm long. Although they were bilateral, the right part of the body was much more involved. The lesions had always been asymptomatic, no pain or pruritus had ever been noted. These macules had appeared about 10 years before, starting on the right arm and then spreading to right shoulder and to the other sites. No preceding inflammation was reported, nor any induration or sclerosis. In the past they had been treated with an emollient cream for keratotic skin for 4 months. Under this treatment regimen, an improvement of the pigmentation was reported by the patient as the macules became less dark, but, after the cream was stopped, the brownish colour relapsed. Personal anamnesis showed asthma and allergic rhinitis in childhood. Family history was negative for skin diseases. Laboratory investigations including blood cell count, blood biochemistry, antinuclear antibody tests, anti extractable nuclear antigen antibodies, antitopohisomerase 1 antibodies, anticentromere antibodies, anti Scl-70 antibodies were all negative or within the normal range. Histological examination of a 4-mm punch biopsy from the right arm revealed a normal epidermis with a hyperpigmented basal layer, overlying a dermis with a thickening of collagen bundles; the skin appendages and the pilosebaceous complexes were preserved. Weigert stain demonstrated unaltered elastic fibres (Figure 2). Moreover, ultrasound imaging was used to evaluate the skin atrophy. The lesional skin in the upper right part of the dorsum revealed a subcutaneous thickness of 1.7 mm vs. 2.9 mm on the controlateral normal skin. In another point, the difference in subcutaneous thickness was even greater: 1.8 mm on the macules and 4.2 mm on the controlateral side. At a 3-month follow-up the skin condition was stable. On the basis of clinical and histological appearance and ultrasound investigation, LAM was diagnosed (3, 5).
Figure 1Figure 1
Slightly atrophic and brownish macules localised along the Blaschko’s lines involved the chest, the axillas and shoulders, running along the right arm in our Case 1.
Figure 2 A–C.Figure 2 A–C.
A) Histological examination of a 4-mm punch biopsy from the right arm of our case 1 revealed a normal epidermis with a hyperpigmented basal layer, overlying a dermis with a thickening of collagen bundles; the skin appendages and the pilosebaceous complexes (more ...)

Case 2
A 70-year-old woman was referred to us because of the presence of a hyperpigmented patch composed of multiple brownish slighly atrophic macules on the right side of the trunk. The skin lesions had appeared 6 months before and had spread progressively, darkened, and grown in number and in size till reaching a maximum diameter of 14 cm and a minimum diameter of 4 cm. This patch was “S” shaped and followed the BL (Figure 3). The patient referred a continuous lumbar discomfort, mild pruritus and moderate pain at night. There were no other clinical symptoms and the remaining physical examination was otherwise normal. Family history was negative for dermatological diseases; the patient had suffered from a contact allergic dermatitis of the face for 30 years due to mica powder (talcum), as she used to work in a chemical factory. She was also afflicted by a lung intoxication with mica powder (talcum) in the 1990s. She had retired 16 years ago. The patient performed a complete check-up, but the results of a complete blood count, coagulation, liver and kidney function, antinuclear antibodies, protein profile, erythrocyte sedimentation rate, and serological tests for Borrelia, Herpes Zoster and Herpes Simplex were all normal or negative. The ultrasound imaging of the abdomen did not reveal any pathology of the urinary and gastro intestinal tract. A skin biopsy was perfomed on the lesional right side of the thrunk and showed a localized hyperpigmentation in the epidermal basal layer, a mild superficial perivascular lymphocytic infiltrate in the dermis and a slight thickening of collagen fibres in the mid reticular dermis without any other pathologic feature. Weigert stain disclosed a fragmentation and decreasing number of the elastic fibres in the dermis. A diagnosis of LAM was established, based on clinical and histopathological findings. An ultrasound examination showed a subcutaneous atrophy, as the thickness of the subcutaneous tissue in the lesional skin was 4.3mm while it was 6.2mm on the controlateral side of the thrunk. We treated the patient with the antihistamine desloratadine 5 mg/day, topical tretinoine 0.05% once a day, and with a moisturizing cream based on glycerin. After one month the discomfort and the pruritus had decreased, and the macules appeared reduced in size and less dark. The patient continued with an emollient lotion and with desloratadine and tretinoine every two days. After 1 year, no more pain is referred and there is just a cosmetic blemish (Figure 4).
Figure 3Figure 3
Multiple brownish slighly atrophic macules on the right side of the trunk in our Case 2.
Figure 4Figure 4
After 1 year there is just a cosmetic blemish in our case 2.

Discussion

The criteria for the diagnosis of LAM originally included: onset during childhood or adolescence; development of hyperpigmented, slightly atrophic, unilateral lesions following BL on the trunk or limbs; absence of prior inflammation or subsequent scleroderma; a stable, nonprogressive clinical course and, histologically, hyperpigmentation of the basal epidermis and a normal dermis with unaltered connective tissue and elastic fibres (1, 4, 6).

So far, 34 cases of LAM have been reported in the literature to the best of our knowledge, including cases with different clinical and histologic findings such as preceding inflammation, collagen sclerosis, teleangiectases, and psoriasiform changes (6, 7) (Table 1).

Table 1Table 1
Cases reported as Linear Atrophoderma of Moulin.

On account of these clinical and histological features not strictly adherent to the original description of Moulin et al. (1), the true number of cases may actually be smaller (2, 3, 6). Thus, some authors proposed atypical variants of LAM, but others assumed that different clinical entities were described as LAM (68). Browne et al. (7, 9) reported a case with antecedent inflammation and they suggested that there are 2 variants of LAM, an inflammatory and a non-inflammatory, or that an antecedent inflammatory phase ultimately may evolve into hyperpigmentation with atrophy. Later, Utikal et al. (7, 8) referred 2 patients with prominent teleangiectatic erythema within the lesions of linear atrophoderma and argued that these cases may represent a novel variety of LAM or a separate entity (8). In our review of the literature, we found cases that differ from the original 5 not only in the histology but also in the age of onset, the localization and the associated conditions. While LAM usually starts in childhood or adolescence, the reports include a congenital case of the leg (2) and 2 cases developed in subjects over 30 years (10, 11). Even though Moulin et al. (1) presented unilateral localizations, in the literature we noted 5 reports of bilateral LAM (5, 8, 9, 12, 13). Furthermore, in most of the patients LAM occurred in the trunk and limbs, but there are 2 patients who presented the disease in the neck (7, 14). Recently, lentiginosis has been found associated with plaques of LAM that were not only hyperpigmented but also hypopigmented (12, 13, 15).

All laboratory findings in patients with a diagnosis of LAM are usually normal except elevated antinuclear antibodies described twice (4, 16). In 2003 Danarti et al. (10) reported 4 cases of LAM, reviewed 15 previously published cases and aimed to distinguish LAM from APP and morphea. The 2 key points suggested for the diagnosis of LAM were: 1) the presence of a hyperpigmented atrophoderma following the BL; 2) histopathological features including a thickening of the collagen bundles and a mild, scattered, chronic inflammatory infiltrate (7, 10). However, Ang et al. (3) subsequently reserved the diagnosis of LAM to the cases that fulfil the criteria originally proposed by Moulin, in particular the lack of pathology at histological examination. They suggested that some of the cases diagnosed as LAM could be appropriately defined as APP that may be linear or may follow the BL, while others may be more appropriately categorized as inflammatory conditions along the BL. Moreover, it was unlikely that the cases involving alterations of the collagen fibers, such as thickening or sclerosis, represent a different stage of LAM (3, 7). Danarti et al. (17) replied to these observations by underlining the concept of mosaicism, which is a common denominator of dermatoses that follow BL but seems not to be present in APP and morphea. They suggested that the different histopathological features of LAM may be due to the examination at different stages of the disorder (17).

The diagnosis of LAM is mainly based on clinical and histopathological findings (18). Moreover, an ultrasound imaging of the subcutaneous tissue represents a helpful tool to measure the thickness of dermis and subcutis (10, 19). In fact, gross histological findings to explain the clinically obvious atrophy are absent and the dermis should be unaltered. Therefore, we believe that the name “atrophoderma” does not correctly describe this condition, as it was originally presented with normal dermis, but it would be better named “pseudo-atrophoderma”.

Our cases match the clinical appearance of LAM, without antecedent inflammation or subsequent induration or scleroderma, and, remarkably, our first patient presents a bilateral involvement and the second is the oldest case ever described (6, 11, 14). The histopathological features found in our biopsy samples have been already described in cases diagnosed as LAM (10).

Differential diagnosis in our cases concerns first a linear post inflammatory hyperpigmentation, that was excluded because there was no preceding signs and symptoms of inflammation, and because of the atrophy and of the longstanding presence of the lesion; last but not least, APP and linear morphea. However, the features found in biopsy specimens show that a differential diagnosis based on a too subtle histology is very difficult. As previously suggested by Danarti et al. (17), we agree that the occurrences that have been described under the umbrella of LAM consist of a group of diseases with different histopathological findings, that are related to examination at different stages of the spectrum of an evolving dermatosis, clinically characterized by depressed plaques following the BL. In fact, there might be a significant clinical and histopathological overlap among LAM, APP and morphoea following BL (15). The correlations between LAM and APP do not seem to have been clarified yet (3, 18). In fact, some authors consider LAM as a variant of APP localized on BL (3, 4, 14, 18, 20) and others present APP as a variant of morphea (8, 21), and also morphea has been described along the BL (22, 23). This may clarify the close relationship among these 3 phenomena, and, considering the overlapping clinical and histological appearance, some cases cannot be classified with complete certainty.

In particular, if we consider the histopathologic findings schematized by Danarti et al. (10) (Table 2), we do not find any significant difference between LAM, the early lesions of APP and the early inflammatory stage of morphea. All 3 conditions present no alteration in the epidermis, a thickening of collagen bundles and an inflammatory infiltrate in the dermis; some differences could be seen in the subcutis, which should be reduced in LAM, unaltered in APP, and with thickened trabeculae in morphea. The older lesions of APP and the late sclerotic stage of morphea have both thickened and tightly packed collagen bundles in the dermis; moreover, in the subcutis there are no alterations in APP, while thick, pale, sclerotic collagen bundles replace the fat cells in the scleroderma, that shows also a loss of pilosebaceous complexes and atrophy of the eccrine glands.

Table 2Table 2
Histopathological features for the differential diagnosis of Atrophoderma of Pasini and Pierini (APP), morphea and Linear Atrophoderma of Moulin (LAM), based on the article by Danarti et al. (10).

It is always difficult to evaluate the subcutaneous tissue, since it is very often missing in the samples of cutaneous biopsies. Furthermore, to correctly evaluate the thickness of the hypodermis, the specimen should include the underlaying fascia, as the subcutis is required to measure the dermis, and obviously a control sample from the controlateral area is necessary. Thus, the correct significance of a histological picture should consider the depth of the biopsy specimen, the stage of the disease, the dermatological anamnesis and follow-up, the somatic characteristics of the subject (skin colour, sex, age) and the localization of the sample, because in some areas of the body, for example, the collagen bundles are normally thickened as in the back or thinned as in the folds.

Therefore, the histology could be indicative of the stage of the disease, but the differential diagnosis should be based and oriented by other clinical factors (Table 3): 1) the localization along the BL, APP do not follow the BL by definition (7), if we do not assume a blaschkolinear variant of APP (3), while morphea could be blaschkolinear (22, 23). 2) The distribution, APP is usually bilateral and symmetrical (10, 21) while LAM is mostly unilateral. 3) The prognosis, APP is progressive (10, 21) while LAM remains stable (1).

Table 3Table 3
Clinical characteristics of Atrophoderma of Pasini and Pierini (APP), morphea and Linear Atrophoderma of Moulin (LAM) (10).

The age of onset and the evolution are not very helpful, because LAM is typical of childhood and adolescence but it has also been reported in later decades, as APP and morphea (10), and the lesions are present for decades in both LAM and APP (10). Therefore, a definitive diagnosis could be reached only with a long follow-up of the patients with multiple biopsies over time. In fact, sometimes at the first examination the differential diagnosis among LAM, blaschkolinear APP or blaschkolinear morphea could be impossible and just speculative, because they seem to belong to the same spectrum (5) of disease.

Different considerations could be made if the histological diagnosis of LAM remained strictly adherent to the Moulin et al. (1) description (i.e. just a hyperpigmentation of the basal layer), but articles published so far demonstrate that there is no general consensus in this way.

In the literature the differential diagnosis of LAM also involves other dermopathies following BL, such as “Linear and Whorled Nevoid Hypermelanosis”, that is congenital or appears in childhood with a pattern along BL and with macular and hyperpigmented morphology, but atrophy is absent (18). Epidermal nevi occur in early childhood or at birth, while Lichen striatus is an acquired disease easily distinguishable clinically from LAM (18). Focal dermal hypoplasia (atrophic and hyperchromic lesions) presents along BL at birth and often exhibits distinctive extracutaneous anomalies (skeletal, ocular) characterizing the Goltz Syndrome phenotype (18).

The pathogenesis of acquired dermatoses localizing along BL has not yet been identified (18). So far, the hypothesis made by Happle (18, 24) that transposable elements may cause similar skin lesions seems to be the most plausible (18). However, this epigenetic mechanism is still an unproven hypothesis in man (18). LAM is thought to be caused by a somatic mutation that takes place early in embryogenesis, resulting in a geno and phenotypic mosaicism similar to other dermatoses following BL (8, 14). However, no gene responsible for LAM has been identified to date (8, 14).

There is no proven effective treatment for LAM. Topical steroids and high dose penicillin have been reported to be ineffective (8, 18). Artola et al. described a patient whose lesions stabilized with oral Potassium aminobenzoate 12g/day (8, 20). Another patient treated with oral penicillin and shower PUVA responded well, but further studies are required (8).

The prognosis of the disease is favorable. As emphasized by Moulin et al. (1) the absence of complications is very important to reassure the patient and to explain that this condition should be a cosmetic blemish only (1, 10).

On the other hand, while Moulin et al. (1) stated that in LAM further examinations and treatments can be avoided, we nevertheless suggest continuing the dermatological follow-up for several years after the first evaluation until a definitive diagnosis is reached. In conclusion, we believe that the term “pseudo-atrophoderma” could better qualify the features of the original cases referred by Moulin et al. (1). We present 2 new cases of LAM, including the first case ever described in the literature occuring in an older subject. In many ways the presentation of our patients appears to be similar to those described as LAM by other authors. However, whether or not our cases represent a genuine form of LAM will depend on how willing we are to expand the definition of LAM and to distinguish it from other entities, which could be part of the continuum of an evolving disease evaluated in different stages. Thus, as the overlapping histology may be not resolutive at first evaluation, only a follow-up for a long period could lead to the definitive diagnosis.

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