**1. Introduction**

The first three cases of lipoatrophia semicircularis (LS) were described in 1974 [1], with further 19 cases in the following years, also in the German literature [2, 3]. The majority of them were female, with band-like depressions symmetrically affecting the anterolateral aspect of the thighs. The lesions were asymptomatic, with normal overlying skin. Histopathological studies—when done—essentially showed destruction of the fat cells, with atrophy of the fatty tissue. No obvious etiology was demonstrated, but an impaired circulation abnormality of the lateral circumflex artery and repeated local trauma were initially speculated [3].

Since then, another report appeared in the English medical literature in 1981 [4], with another three cases, and subsequently worldwide, including Belgium, France, Italy, Japan, Netherlands, Spain, and the U.S.A., thus being considered an emerging pathology.

Its prevalence ranges from 25 to 37% of office workers, affecting preferably women in their third or fourth decades of life, with women to men rate of about 6/1 [5]. In other series of 74 cases, the prevalence was 16.48%, with an age average of 49.18% [6]. In only one reference a different rate was collected: 55 cases of LS were detected among over 3000 employees in five buildings of a bank in Madrid (Spain); the prevalence was 1.8% and the female/male ratio was 2.3/1 [7].

#### **2. Etiopathogenesis**

Some initial isolated reports were reasonably attributed to local trauma, such as the place of support on a thigh of a bucket for collecting vegetables [8], leaning against desks [9, 10], ironing boards, bath's border for washing [11], dresser with mirror [12] or wash bowl while applying make-up [13–15], knocking against the edge of the laundry [16], resting against the counter [17], crossing legs beneath the office desk [18], wearing tight jeans, trousers (**Figures 1** and **2**) or girdle [11, 19–22], or hold-up stockings [23], frequent use of sports tights [24], elastic bands [25] or hosiery with an elastic component [18], or appearance of lesions some weeks after the introduction of a new chair at office work [26]. Interestingly, in the case described after wearing tight jeans [19], the same authors described identical lesions a year after in a sister of their initial patient, who developed them after wearing the discarded jeans [27]. Also illustrative of the action of a mechanical pressure was the fact that the lesions spontaneously disappeared during summer and reappeared at the same place during winter, months in which the affected female patient wore hosiery with an elastic component [18]. However, there are also some reports in which no trauma was identified [4, 28, 29], even with spontaneous resolution of lesions [30].

The lesions affecting forearms have been attributed to tight sleeves of underwear [31] or tucking up skirts and leaning over tables, or hard surfaces [32]. A single case of multilocular and rapidly progressing lesions affecting the trunk and limbs was reported in a 51-year-old adipose patient [33].

There are few descriptions of LS in infancy [34–36], with the exception of a supposed outbreak of cases of LS in a public school in Barcelona, which caused great alarm, but that finally proved to be an epidemic somatoform disorder [37]. In isolated reports, diverse and probably fortuitous cases of LS have been described in association with systemic lupus erythematosus and methotrexate injections [38], after intragluteal injection of benzathine penicillin [39], Behçet disease [40], Sjögren syndrome [41], incomplete CREST syndrome [42], multiple sclerosis [43], segmental dysfunction of the third ipsilateral lumbar root [44] and in relation with a homolateral tibial cyst [45].

The first description of a series of patients working at the same place was done in the Netherlands, after sending letters to 100 employees of the firm in which the initial case was observed [26]. Ten cases were detected, all of them were female, with lesions of LS in their thighs, mostly bilateral. The lesions had appeared several weeks after the chair of their working office was replaced for another with a slightly elevated front edge, which exactly corresponded to the localization of lipoatrophy (higher in short women as they sat further forward on the chair). In all but one patient, the lesions resolved after the chair was changed again. It was also stated that the manufacturer of that chair had received complaints from other companies where the same chair was used.

#### **Figure 1.**

*Typical distribution of LS with two parallel semicircular and depressed bands on the thigh (with permission of John Wiley & Sons Copyright Clearance Center, License No. 5282800364186, April 5, 2022).*

#### **Figure 2.**

*The depressions perfectly match with prominent folds formed by trousers while sitting (with permission of John Wiley & Sons Copyright Clearance Center, License No. 5282800364186, April 5, 2022).*

A few years after, a sitting posture or pressure of the seat surface of chairs study was done in office workers, including electromyographic and pressure measurements, and video analysis [46]. Considerable postural differences were detected in the LS group of employees (21 subjects, 3 male and 18 female, 11 of them diagnosed as having LS), including less use of the lumbar support of the chair, static postures while sitting and too high sitting surface of the chair.

Other report of collective cases was done in France in the year 2000, with four index cases affecting young women, most of them working at desks in the same company. The company, a telecommunication enterprise, had recently moved to a new office with salient-edged furniture, all desks measuring 70 cm high and 1 cm thick. The active and dynamic young staff often stand up leaning on their desks to exchange files with colleagues sitting in front. Having this data, 58 out of 65 employees were examined: a total of 18 cases of LS were detected, 15 cases with bilateral depressions of their thighs, affecting 12 women and 6 men; the height of the lesions was constant and it was the same as the height of the desk, 70 cm [47]. Similarly, a year before, seven cases were reported from London (one man and six women working at the same office) in which the most logical explanation for the origin of lesions was repetitive trauma on their highs produced by the sharp edge of the desks [48]. Other 55 cases of LS were detected in a Spanish company from a total cohort of 3055 employees [49]. A case–control study was done, including 39 females and 16 males; all lesions were located on the thighs. Only female sex and leaning the thighs over the edge of a table were the two variables that showed a statistically significant relation with LS after logistic regression with *x*<sup>2</sup> adjusted for age and sex. No statistically significant relationship was found with weight, height, body mass index, wearing jeans, clothing fibers, or autoimmune diseases.

The outbreak of cases, first in a Belgian bank insurer [50], and later in Barcelona (Spain) [51] added enough reasons for considering an environmental origin. Belgium cases presented after bank employees moved to a new building equipped with new furniture and data cable but kept most computer equipment; 6 months later 135 individuals had developed LS, reaching 900 cases in a period of about 8 years. Brussels cases finally involved 1300 office workers in a bank over a 12-year period, and the cases from Barcelona reached 1137 subjects from February 2007 to October 2008 [51]. Concomitant series of patients began to appear, adding new information to the process. In that sense, seven cases of LS (six women and one man from a total of 16 workers equally distributed by sex) were reported after an enterprise made a building reform [52]. The cases of LS appeared between 6 and 8 months after using the new installations. The median age was 39 years, and the lesions were bilateral in three cases and unilateral in four. The lesions were located on their thighs, between 72 and 74 cm up from the floor. Environmental working conditions were analyzed. Relative humidity varied from 32 to 45%; magnetic and electrical field measures were not optimum. As corrective measures, the humidity was raised to 55%, chairs were changed to optimal ergonometric features, electrical resistance, and ground-mass electrical discharge from metallic structures were improved. After 12 months, clinical and echographic evaluations were performed: four patients had completely improved and three had recovered between 40 and 70% of the adipose lost.

Small series of cases have been reported intermittently, describing female office employees [53], sometimes working at "intelligent buildings" or over metallic desks equipped with computers [54], or affecting males sharing the same working desk [55].

#### *Lipoatrophia Semicircularis DOI: http://dx.doi.org/10.5772/intechopen.105920*

With hundreds of affected patients, it became obvious that LS was office-job related, occurring preferably in female administrative employees, about 6 weeks or more after moving to a new "intelligent" or renovated building; these were equipped with modern-design furniture (chairs and desks), where personnel worked in proximity with numerous electric devices equipped with new data cables, such as computers, printers, and telephones among other. Thus, an electromagnetic theory was outlined, but without discarding that mechanical pressure may act as a facilitating factor [56]. It was detected that electric fields beneath the desks were higher than the normal background; also, a higher superficial electric resistance on working tables and desktop devices was noticed, resulting in an electrostatically charged desk. Consecutively, after coupling with a conductor (employee thighs, 72 cm up from the floor) a discharge was produced on that zone. A dry atmosphere from air conditioning and a low environmental humidity add favorable factors for electrostatic discharges. Therefore, LS may be produced by activated macrophages through electrical stimulation. Macrophages release cytokines, including tumor necrosis factor alpha (TNF-α), provoking direct damage of adipocytes. New chairs may be a contributing factor, acting by compression pressures and push-up forces on the posterior zones of the thighs, thus inducing a reduction of anterior blood flow which could make fatty tissue more vulnerable [56]. In further publications, the same authors in a step-bystep analysis of all presumed causes of LS, conclude as a hypothesis that it originates from a high electric field between the desk and the legs of the individual and that electrostatic discharges are not necessarily involved [57]. They also point out that some people may be more sensitive than others, employing the term "electro-hypersensitivity." In another *in vitro* study, they used the alkaline comet assay to investigate DNA damage in different cells exposed to strong electric currents. They found that adipocytes were more vulnerable, presenting more DNA damage than other cells, including macrophages and white blood cells. In a second experiment, it was found that the blood of LS patients showed statistically significant DNA damage in white cells after electrostimulation, in contrast with controls without LS [58].

All the electric parameters of the skin (potential energy, impedance, electric energy conservation, and resistance) are susceptible to be influenced by electric fields, with biological repercussions [59]. Electroactivation of macrophages has been reported *in vitro* through several frequencies of electromagnetic fields [60]. It has also been demonstrated that exposure to weak power-frequency, magnetic fields can adversely affect the lipogenic process; by means of an intermittent exposure to a 50 Hz magnetic field of 100 μT for 42 hours, it was observed a significant reduced cytoplasmatic lipid content of human adipose tissue stem cells [61]. In a preliminary experimental study *in vitro*, the same investigators reported the potential action of weak magnetic fields on adipocyte differentiation, with a significative descent of fatty acid synthesis and inhibition of mechanisms involved in adipocyte differentiation; magnetic field exposition induces changes at intracellular signaling pathways through blocking of p-ERK1/2 (extracellular signal-regulated kinase 1 and 2), inhibiting the expression of the differentiating factor PPARγ (peroxisome proliferator activator receptor-gamma) necessary for the progression of adipocyte differentiation [62]. All these findings support the hypothesis that magnetic fields may be involved in the origin of LS.

On the other hand, other authors have concluded that electrostatic charges, but not electromagnetic ones are mainly involved in LS [63]. In a company of 390 workers, 42 women had lesions of LS, mostly located on the anterior thighs. A technical study of the building was performed, where no abnormal electromagnetic measurements were found. On the contrary, electrostatic findings and occupational behaviors were found to be relevant. Fifteen patients suffered discharges after touching objects, 14 wore pants and 12 synthetic fibers among other clothing types. All furniture was appropriately grounded and showed no electrostatic charges, while chairs did. No electrostatic accumulation was found in screens and carpeted floors, but certain footrests, the output of printers, and printed sheets from laser printing and copiers were electrostatically charged. Environmental relative humidity was closer to 45%. The sum of all these factors, favored by the common use of footwear containing rubber or synthetic soles, clothing with silk, rayon, wool, or synthetic fibers, facilitate static charge accumulation; this usually discharges to the ground in those areas with higher contact pressure, especially through contact with the desk, a phenomenon that occurs several times during office work. This area is the anterior part of the highs, especially in women wearing pants that are more adjusted at this zone, and also acting on a fatty tissue different from males. A quite interesting observation was the fact that two cases presented with lesions about 10 cm above the knees, in contrast with the more common location on the thighs, 72 cm up from the floor; they were the only two employees who regularly wore skirts, in which their end parts coincided with the location of lesions of LS. They also concluded that people at risk were mainly women wearing synthetic clothes, in special short-sleeved shirts, pants, and footwear with rubber soles. Men infrequently wear adjusted clothes and preferably wear longsleeved shirts, which facilitates dispelling the electrostatic charges through the desk, bypassing their bodies [63].

A recent study was done between 2018 and 2021 comprising 449 office workers from the same public institution at different buildings in Barcelona (Spain) [6]. The prevalence was 16.48%, with 74 cases detected (71 women and 3 men). Most of them were between their 40s and 50s, with the majority of lesions located on the thighs. With 80% of employees working from home ("teleworking") during the peak of Covid19 pandemic between 2020 and 2021, only 23% showed the disappearance of LS lesions, which was not statistically significant. No clear reason was found, but it was suggested that perhaps the same working conditions were present at home. Body mass index was also not relevant in the disappearance of lesions.

## **3. Clinical findings**

LS is characterized by depressed areas on the skin surface, with distribution in long, horizontal, and generally symmetric bands located on the anterolateral aspects of both thighs in 89.5% of cases, and usually located at 72 cm from the floor, representing the usual height of office desks. Interestingly, in the case of a very tall worker (1.95 m height) who elevated 20 cm on the table of his desk for recurrent lumbalgia, the depressed band appeared at 92 cm from the floor [64]. Similarly, in a series of 10 cases, shorter women had higher lesions up the thighs [26].

The lesions are flesh-colored, barely visible in incident light, and usually asymptomatic (85.5%) [65]. Depressions are semicircular, transverse, often as bilateral and symmetrical bands, 5–20 cm long, 2 cm in width, 1–5 mm in depth [66], and no pigmentation is present. When more than one is present, they appear in a parallel arrangement. The overlying skin is normal and there is no history of preceding inflammation.

Lesions are usually, but not always asymptomatic. When present, local symptoms are mainly described as pruritus (sometimes a week before lesions appear) [66], tired and heavy legs, paresthesia, cramps or pain (mainly overnight) spontaneous and/ or after exercising. In a minimal percentage of cases, general symptoms have been reported, including asthenia, myalgia, and headache. However, in a case series from Barcelona, 26 patients from a total of 34 (76.4%) presented accompanying symptoms: the most frequent sensation of cramps when in contact with metallic objects in the office (like door handles), and heavy legs [67].

No associated features are seen, and distal edema has not been described.

It mainly affects women in their 20s or 30s [22]. The differences observed in the female-to-male ratio (6/1) may be due to a greater proportion of subcutaneous fat in females, predisposing to this condition. Physical constitution and hormonal changes during pregnancy may contribute to the development of LS. Women as well are more likely to present to a medical practitioner with this condition because of cosmetic concerns [22].

The median time for the development of the lesions is 2.5 months. Lesions disappeared spontaneously over a ranging period of time from 9 months to 4 years after some cause is identified and remedial action is taken [22]. Location of lesions has been also described in other areas, such as posterior and inside thighs, trunk, or upper limbs [65].

#### **3.1 Classification based on diagnostic criteria**

Recently, Bru-Gorraiz et al. [65] have proposed a classification of LS based on clinical features:

Type I. Typical LS: Bilateral and symmetrical lesions involving the anterior or anterolateral surface of the thighs. Horizontal bands with length at least three times the width.

Type Iu. Unilateral LS: Similar to type I, but unilateral.

Type II. LS in bands on the lower limbs. Length of lesions is at least three times the width.


Type III. Nonspecific lipoatrophy.

III a. Other locations (hips, face, upper limbs, and abdomen).

III b. Other morphology (round and oval). Length is two times the width.

Clinical outcomes are more favorable in the first two groups where 76% of patients showed total or partial improvement of the lesions, *versus* 25.8% of the last two groups [65].

#### **4. Diagnosis**

The diagnosis is essentially clinical, considering the presence of bands related to the height of furniture or related to repeated micro traumas. These bands can be visible or palpable.

Laboratory exams or complementary investigations are not necessary for this diagnosis, except to establish differential diagnosis in patients with suspected connective tissue disorders. Antinuclear antibodies, anti-DNA, anti-SCl-70, C3 and C4 complement fractions, rheumatoid factor, and other routine blood, and biochemistry analysis have always been normal when done.

However, in 2013 a case–control study was done in 21 cases of LS from Madrid [68], in which serum adipokines (leptin, chemerin, and vaspin) and high sensibility C-reactive protein (hs-CRP) were analyzed. Statistically significative differences were found in LS cases, with raised levels of hs-CRP and leptin, and low chemerin. The authors conclude that there is an underlying inflammatory process in LS, affecting adipocyte differentiation. Leptin is the main adipokine; its functions include energy homeostasis and also stimulation of lipolysis; chemerin participates in producing mature adipocytes. No further publications have been done in this respect.

## **5. Histopathological findings**

Regarding histopathology in cases of the so-called idiopathic localized lipoatrophy [69], two patterns have been described, involutional and inflammatory. The most common is the involutional type, in which adipose tissue is present but abnormal. Lobules of fat are well-defined, various sized, varying from small to medium-sized lipocytes on a background of hyaline material. Lipocytes are in general smaller than normal, have a more prominent nuclei and often appear with a rounder shape. The lipocytes appear embedded in hyaline material varying, from sparse to abundant. Capillaries are numerous. In some cases, the involutional changes are more evident at the periphery of the lobule and look normal toward the center. Individual mononuclear inflammatory cells are occasionally seen. Different staining show scattered, fine, curled elastic fibers within the lobules in the hyaline zone. Focal mucin-positive cells can be seen in the perivascular location in some cases. On the other hand, the inflammatory pattern shows normal appearing lipocytes, a normal vasculature, and scattered aggregates of lymphocytes, histiocytes, and plasma cells on a background of hyaline degeneration in broad areas of the fat, similar to lupus panniculitis or traumatic panniculitis [69].

In LS most patients have refused biopsies. When done, these have essentially shown a partial loss of fat, sometimes replaced by new collagen [30], and absence of panniculitis signs. In one case a nearly complete loss of adipose lobules was reported, without signs of inflammation or fibrosis [70]; other cases have shown loosely dispersed fat lobules with medium-sized adipocytes [14], decreased size of adipocytes with intermingled eosinophilic and hyaline material and some histiocyte and lymphocyte infiltration [20, 40], mild accentuation of interlobular septa with atrophy and centrilobular fibrosis of some adipocytes without inflammation [23], hemorrhage in the fat tissue compatible with panniculitis [16], complete loss of adipose tissue [34] and involutional adipocytes, numerous capillaries, and a sparse lymphohistiocytic infiltrate with calcification [36].

The immunohistochemical study has been done only in one case, showing adipocyte positivity for vimentin and S-100 protein, with few positive histiocytes for CD68 [20].

It has been questioned if three histopathological patterns exist (involutional, inflammatory, and "normal") or if they represent different stages of localized lipoatrophy depending on the time in which biopsies are taken [14].

Histopathological features in some cases have shown normal findings [41, 71].

#### **5.1 Ultrastructural features**

In a report of two cases, adipocytes abnormalities, fibrillogenesis, and sclerosis were noticed in one case, while the other with persistent lipoatrophia showed rarefaction of collagen fibers [11]. An electron microscope study was also done on one patient with LS and Behçet disease [40]. The images showed fat-laden macrophages with lysosomes, numerous fat droplets, and electron-dense granules in the cytoplasm. Lymphocytes were found in the detachment produced between the fat and basal lamina. A complete loss of the basal lamina beneath the adipose layer was described. The cytoplasm of the fat cells was vacuolated.

## **6. Other studies**

Ultrasound of the affected zone is not always conclusive, sometimes with negative findings, although visible and palpable lesions exist [41, 66]. On other occasions, it has shown an important subcutaneous loss [72]. Ultrasound imaging of the semicircular depression has revealed a preserved epidermis and dermis, with a focal decreased thickness of the subcutaneous tissue [71, 73], or slight compression of the adipose tissues [14] in the same axis of the visible site of atrophy. An increased echogenicity of the subcutaneous tissue can be present [74]. Illustrative findings of a case are shown in **Figure 3**.

High-frequency longitudinal sonography shows similar findings, with a reduced thickness of subcutaneous tissue and a slightly fibrotic component [25].

Magnetic Resonance Imaging (MRI) has shown a loss of the superficial subcutaneous adipose tissues in four cases. No alteration in the thickness of subcutaneous septa was found and fat lobules were normal in size and shape [31, 53, 75, 76]. No alterations were found in subjacent muscles in another report, and the focal atrophy of subcutaneous fatty tissue was not replaced by fibrous or other types of tissue [72]. In other cases, the subcutaneous tissues of the thighs were normal, but the muscles under the affected area were slightly indented [22]. Sometimes the subcutaneous tissue and muscles have shown normal findings [15].

Electromyography has been normal when done in a few cases [31, 32, 47, 76]. Nevertheless, surface electromyography measurements of the quadriceps in six subjects with LS and five without, showed a more constant static pattern in muscle activity in LS individuals, contrasting with a more dynamic pattern in those without LS, thus confirming that LS people adopt more static postures at office work [46].

Ultrasound and MRI are useful to differentiate lipoatrophy from other alterations of fat tissues. Panniculitis shows thickening of interlobular septa with smaller fat lobules. In lipoatrophy interlobular septa and fat lobules are normal and a loss of superficial fat tissue is present [20].
