Idiopathic Localized Involutional Lipoatrophy: A Retrospective Study of 12 Cases.

BACKGROUND: Idiopathic localized involutional lipoatrophy (ILIL) is focal loss of subcutaneous tissue without any clinical or histopathological inflammation with spontaneous regression.
OBJECTIVE: To retrospectively study clinical features and evolution of lesions in patients diagnosed with idiopathic localized lipoatrophy presenting to the department of dermatology of two district hospitals of Himachal Pradesh.
MATERIALS AND METHODS: A retrospective study of clinical patterns and evolution of ILIL was done in patients presenting with this condition in two district hospitals in the past 4 years (October 2013-September 2017). All clinically suspected and histopathologically confirmed cases of idiopathic localized lipoatrophy were included in the study. All cases with history of antecedent injections, vaccination, or medications before the development of lesion and inflammatory lipoatrophy on histopathology were excluded.
RESULTS: We found a total of 12 patients with ILIL. About 66% were children (8/12), 3 (25%) young females, and 1 (8%) young adult male. The most common site involved was buttock in 9 (75%) cases followed by a single case each (8%) with lesion on arm, face, and lower back. Two children and one adult were having bilateral involvement (25%), whereas the remaining had unilateral lesions. Lipoatrophy in 8 (66%) patients decreased spontaneously (with placebo) within 4-12 weeks duration whereas 4 required treatment. None required surgical or cosmetic interventions. LIMITATIONS: Small sample size and nonavailability of immunohistochemistry reports in all patients.
CONCLUSION: ILIL is a rare form of lipoatrophy with specific loss of adipose tissue without any inflammatory changes. We concluded that ILIL is an underreported entity, probably due to its spontaneous resolution.

Introduction

Idiopathic localized involutional lipoatrophy (ILIL) is a rare distinctive form of localized lipoatrophy which arises spontaneously and is of unknown etiology. It is characterized by specific focal loss of adipose tissue without antecedent inflammation.[1] A majority of the studies reported in literature have described inflammatory localized involutional lipoatrophy with history of previous injections, drugs, or trauma. To the best of our knowledge, there are no studies that have described true idiopathic variant of localized involutional lipoatrophy in a significant number of cases.

Materials and Methods

We conducted the study by retrospectively collecting clinical data of all cases diagnosed with localized lipoatrophy with minimal or no inflammatory changes on histopathology, who reported to the department of dermatology in two district hospitals, in Himachal Pradesh during the past 4 years (October 2013–September 2017). Records of clinical histories, histopathological staining by haematoxylin and eosin, and immunohistochemistry for CD-68 were reviewed. We included all clinically suspected cases [Figure 1] of ILIL with characteristic histopathological findings (unremarkable or thinned out epidermis, absent or sparse perivascular lymphohistiocytic infiltrate with minimal or moderate hyalinization of dermis, and characteristic diminished fat lobules in subcutaneous tissue without inflammation) [Figure 2a]. Immunohistochemical staining record was found in only five patients, which showed CD-68-positive macrophages [Figure 2b].

Figure 1

Depressed, depigmented plaque on buttocks of a child

Figure 2

(a) (Hand E ×40) Diminished fat lobules. (b) CD-68-positive immunohistochemistry

Routine hematological and biochemical investigations along with fasting blood sugar, HbA1C, thyroid function tests, antinuclear antibodies, and human immunodeficiency virus (HIV) tests were performed in all patients. Patients with associated autoimmune diseases (lichen sclerosus et atrophicus, morphea, or lupus profundus), personal or family history of diabetes, thyroid and other systemic disease, and with HIV-positive status were excluded from the study. None had history of antecedent injections, vaccination, or medication before the development of lipoatrophy. All children had completed immunization at 18 months of age according to National Immunization Schedule.

Results

After compilation of all records, demographic and clinical data were summarized as below [Table 1].

Table 1

Clinical details of 12 ILIL patients

Age (years)	Sex	Duration of disease (weeks)	Site	Size (cm)	Unilateral/bilateral
2.5	M	3	Buttock	3.5 × 2 (left) 3 × 2 (right)	Bilateral
3	M	4	Buttock	4 × 2.5	Unilateral
3.2	M	3	Buttock	3 × 2	Unilateral
4	M	2	Buttocks	4.5 × 2.5 (left) 2.5 × 2.5 (right)	Bilateral
5	M	13	Buttock	2.5 × 2	Unilateral
8	M	4	Buttock	5 × 3	Unilateral
15	M	3	Buttock	12 × 2.5	Unilateral
17	M	4	Buttock	14 × 3.5	Unilateral
19	F	2	Arm	2 × 2	Unilateral
22	F	3	Lower back	5 × 3.5	Unilateral
26	F	3	Buttock	1 × 1.5	Unilateral
28	M	16	Face	2.5 × 2	Bilateral

Eight (66%) of 12 patients were children, and 5 (41%) were less than 5 years of age. The youngest child was of 2.5 years of age, whereas the adult with face involvement was 28 years of age [Table 1 and Figure 3]. The median age of presentation was 11.5 years. Three (25%) patients were females (adults), whereas 9 (75%) were males (8 children and 1 adult). The duration of disease was less than 2 months in 10 (83%) cases (patient with lesion over arm presented in 2 weeks) and 4 months in 2 cases.

Figure 3

Bar chart depicting demographic profile of patients

Two siblings, one having arciform lesion and the other with oval lesion over buttock, were seen (cases 6 and 7). None of the other patients had history of such lesions in the family. Size of the lesion varied from 1.5 × 1 cm to 14 × 3.5 cm. Most lesions [9 (75%)] were circular/oval in shape, and one patient each had arciform (case 7), linear (case 8), and triangular [Figure 1] shaped morphology (case 2). The most common site involved was buttock in 9 (75%) cases. Arm, lower back, and face were involved in one patient each.

All except one (case 12) patient had depigmentation (91%) over lipoatrophic plaque. Unilateral lesions were seen in 9 (75%). Two children had bilateral, symmetrical involvement of buttock and one adult had bilateral involvement of face.

Lesions in 8 (66%) patients decreased spontaneously [Figure 4] within 4–8 weeks period with placebo. Among those who were not showing any signs of regression at 4 weeks, two of them were started on topical tacrolimus and two (increased in size) on oral corticosteroids. The patient on topical tacrolimus responded in 12 weeks. One patient on oral corticosteroids improved within 12 weeks, whereas the other was lost to follow-up.

Figure 4

Regression of lesion in three patients at 4 weeks

Discussion

Lipodystrophy is a heterogeneous disorder characterized by atrophy and infrequently hypertrophy of adipose tissue. Lipoatrophy and lipodystrophy are often used interchangeably.[2] Lipoatrophy refers specifically to selective loss of subcutaneous fat without exudative reaction or fibrosis. Lipoatrophy may be acquired or inherited. Acquired lipoatrophy may further be classified as generalized (Lawrence syndrome), partial (Barraquer–Simons syndrome), HIV-associated, or localized.

Acquired localized lipoatrophy can be idiopathic or caused due to various types of insults to subcutis, for example, repetitive trauma, pressure, abscess, localized connective tissue disease (lupus profundus, panniculitic lymphoma, morphea), systemic autoimmune diseases (systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, nephritis, thyroiditis, etc.).[34] It may be iatrogenic, often involving areas of antecedent intramuscular, subcutaneous, or intra-articular injections such as insulin (non human), corticosteroids, antibiotics (amikacin, benzathine penicillin), methotrexate, bleomycin, iron, heparin, vaccines, growth factors, and glatiramer.[25678] Localized lipoatrophy without any triggering factor such as injection or injury at the involved site is labelled as idiopathic.

Pathogenesis of localized lipoatrophy is still an enigma. The activated macrophages are supposed to trigger immunologic disorders by secreting a variety of cytokines such as fibroblast growth factor-2, platelet-derived growth factor, interleukin-1, tumor necrosis factor-α, and transforming growth factor-β, resulting in involution of subcutaneous fat tissue.[9]

Peters and Winkelmann[10] first reported localized involutional lipotrophy (LIL) in 1986. Since then more than 30 cases of LIL have been reported worldwide.[11] Dahl et al. in 1996 observed the distinct histological pattern of adipocytes and classified the variant as ILIL.[1] ILIL is a rare condition characterized by asymptomatic lipoatrophy on one or few sites, occurring without any triggering factor and regressing spontaneously within a few months.[12] However, in inflammatory lipoatrophy, multiple lesions of lipoatrophy with histopathological findings of normal lipocytes associated with diffuse infiltrate of lymphocytes, histiocytes, and plasma cells in fat lobules is seen.

Histologically, ILIL lesions are marked by involution (simulating embryonic adipose tissue) which is characterized by small adipocytes embedded in hyaline connective tissue with many capillaries and non- or pauci-inflammatory cells in the subcutis.[13] We included histopathologically proven cases of ILIL. Immunoreactants in ILIL are positive for macrophages CD-68 only and negative for T-cells and B-cells.[14] In this study, immunohistochemistry for CD-68 was positive in all five patients (seven refused for investigation).

Histopathologically, LIL has to be differentiated from morphea which shows much more pronounced inflammatory infiltrate in subcutaneous fat, and trabeculae subdividing the subcutaneous fat are thickened because of inflammation and deposition of new collagen.[15] In lichen sclerosus atrophicus[16] epidermal atrophy, interface dermatitis, collagenization with marked edema in upper and mid dermis is seen and the subcutis is spared. Electron microscopic analysis in ILIL reveals macrophages becoming lipophages.[17]

LIL has more commonly been reported in young females. Yamamoto et al.[14] in 2002 reported six cases and Dahl et al.[12] in 1996 reported 16 cases of LIL, all were females. In both these studies, the majority of patients had history of some injections, as mentioned by Lee et al.[18] in 2010, and should not be confused with ILIL (idiopathic form). In this study, we described 12 cases of ILIL without any history of antecedent injections or significant triggers. Childhood cases reported in literature are rare, and the maximum cases reported were young adults (females). There is single case report of childhood (5 years)[19] and elderly involvement at 67 years of age;[1] however, we had more number of children when compared with adults. Sites commonly involved are arms, buttocks, thighs, and abdomen in most reported cases. Buttocks were the more commonly involved site in our patients and lesions were large in buttocks compared with arms. We assume that buttocks are the commonest site because of repeated trivial trauma and pressure effects. The size of lesions was independent of age and sex. Most of the cases are sporadic except two reports describing ILIL in siblings.[9] Two of our patients were also siblings, though the reason of similar lesions in siblings at the same time is not known; probably some genetic factors may be responsible or any common environmental trigger in a family. ILIL has been reported with a duration of 2 weeks to 1 year[9] before a patient presents for medical examination, probably due to asymptomatic nature of the entity and unnoticeable sites of involvement; the majority of our patients presented less than 4 weeks of duration. Early reporting in our case could be because our patients had skin type 3 and 4 so pigmentary changes become more easily visible. Three of our cases had bilateral and symmetrical involvement as reported by Pai and Pai.[20]

ILIL resolves spontaneously in majority of patients. Anti-inflammatory agents such as steroids, calcineurin inhibitors, and antimalarials can be used in the initial phase when a lesion is expanding.[20] In long-standing lesions which persist fillers can be used to improve cosmetic outcome. All our patients were given placebo and followed after 4 weeks. There was a decrease in size of atrophic lesions in 8 (66%) patients which were continued on the same plan, whereas the remaining 2 were put on topical tacrolimus and 2 on oral corticosteroids at 4 weeks. In a majority (66%) of the patients, lesions regressed spontaneously without any relation to age, location, and size of lesion.

Limitations

As this study included cases from two district hospitals from a hilly state, the true epidemiology of the disease cannot be stated. Immunohistochemistry report of all patients was not available and all cases could not be followed till complete resolution.

Conclusions

ILIL is considered a rare entity. A significant number of ILIL cases in a limited population over a short period of observation in this study challenges its rare status and underreporting may be due to sites involved and spontaneous resolution. Further studies are required with ultrastructural investigations to elucidate the mechanism of diminution of lipocytes without any trigger.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.