An enlarging tender skin depression in a young adult female

What is known about this subject in regard to women and their families?

• Several localized lipoatrophies demonstrate a strong female sex bias.

• Furthermore, some of these disorders also feature worse metabolic complications in females.

• Currently, it is not known why this female sex bias exists. Contributing factors may include genetic, hormonal, and metabolic differences, among others.

• Additional work is required to better understand the pathomechanisms of lipodystrophies.

What is new from this article as messages for women and their families?

• Idiopathic localized involutional lipoatrophy is a rare but often self-limited skin disease.

• Early recognition may prevent unnecessary invasive tests and therapies.

• Contributing factors to idiopathic localized involutional lipoatrophy may include female sex and underlying inflammatory conditions.

Introduction

Idiopathic localized involutional lipoatrophy (ILIL) is a rare condition characterized by a focal fat loss without significant inflammation or identifiable etiology.¹ Given the limited number of cases reported in the literature, the clinical course and management of ILIL remain poorly understood. We present a case of ILIL in a young woman with rheumatoid arthritis (RA).

Case

A 22-year-old female with well-controlled RA on hydroxychloroquine for the past 6 years presented with a 5-month history of a tender, enlarging depression on her right lower back. At the time of presentation, she was also on etanercept, but the development of the lesion preceded initiation of Enbrel by one month. She denied trauma or injections to the area, and etanercept injections were not administered at or near the site of depression. She reported carrying her phone in her back pocket a few times in a month and could not recall additional sources of pressure to the area. Prior treatment with tacrolimus ointment and topical steroid was ineffective. Examination revealed a violaceous, 5 cm × 5 cm round, well-circumscribed, atrophic depression (Fig. 1A). ANA, ENA10, and dsDNA antibodies were negative. Review of a biopsy specimen from 5 months prior revealed atrophy of peri-eccrine fat without collagen hyalinization. A second punch biopsy was performed at our initial visit, 5 months after the development of the lesion. This biopsy of the lesion periphery revealed lipoatrophy without evidence of panniculitis or morphea (Fig. 2A). CD68-positive macrophages were identified via immunohistochemistry (Fig. 2B).

Fig. 1.

Well-circumscribed, round, atrophic depression measuring 5 cm × 5 cm at her initial visit (A) and 5.5 cm × 6 cm at subsequent visit 3 months later (B). (C) and (D) demonstrate spontaneous improvement in the cutaneous depression 4 months and 8 months after the initial visit, respectively.

Fig. 2.

Histopathologic examination. (A) The subcutaneous fat lobules are markedly atrophic, consisting of shrunken adipocytes without an associated inflammatory infiltrate (hematoxylin-eosin stain, 8×). (B) CD68 immunohistochemistry highlights a few macrophages within the atrophic adipose tissue (8×).

Three months after our initial evaluation, the patient reported expansion of the lesion with central tenderness radiating outwards (Fig. 1B), 30 lb weight loss, and worsening joint pain. The patient associated the increased tenderness of the cutaneous depression with worsening of her arthralgias. A third biopsy was performed at the lesion periphery, 8 months after the appearance of the lesion, which showed atrophy of adipocytes along the periphery of the subcutaneous fat lobules, while the central adipocytes were of relatively normal size. No macrophages were identified. Consideration of mycophenolate mofetil was entertained but deferred due to spontaneous improvement in size and depth of the initial lesion within a month following the third biopsy (Fig. 1C and D). Despite improvement in the cutaneous depression, the patient continued to endorse intermittent joint pain.

Discussion

Lipodystrophies are a group of inherited or acquired conditions and can be classified as generalized, partial, or localized.² While the majority result from trauma, injections, or inflammation such as panniculitis, ILIL has no identifiable triggers.^1,3

ILIL typically affects the proximal limbs and buttocks, with the buttocks being affected in up to 75% of cases.^1,4 Histopathologically, ILIL is characterized by absent or shrunken fat cells and a lack of inflammation, although panniculitis may be observed in early stages.³ Several reports have highlighted the presence of CD68-positive macrophages, proposing a role for these cells in fat lobule involution.⁴ Spontaneous regression is common. Thus, an initial period of observation may be appropriate. In refractory cases, immunosuppressants, such as topical calcineurin inhibitors, or systemic intervention with antimalarials or glucocorticoids have been reported to be helpful¹

Our case highlights ILIL in a young female, aligning with literature suggesting a female sex bias in localized lipoatrophies.^1,3,4 Females with select lipodystrophies may also have increased metabolic complications.⁵ Contributing factors may include physical, genetic, hormonal, and metabolic differences.⁵ Additional research is required to better understand the mechanisms underlying sex biases in lipodystrophies.

Similarly, it is unclear whether our patient’s history of RA was contributory. Autoimmune conditions have been linked to other acquired generalized and localized lipodystrophies.² It is plausible that an immunological response to adipocyte antigens leads to macrophage infiltration, cytokine release, and adipocyte destruction.^2,3 To our knowledge, this is the first case to describe a patient with both RA and ILIL.

In this patient, we also did not observe a correlation between the cutaneous depression and the initiation of etanercept therapy. Etanercept was commenced approximately 1 month following the onset of the skin lesion and was not administered in the proximity of the affected area.

ILIL is rare, but it is likely under-reported given its frequently self-limited nature.¹ Additional studies are required to better understand the risk factors, clinical spectrum, and management strategies for ILIL. Earlier recognition may prevent unnecessary invasive tests and therapies.

Conflicts of interest

None.

Funding

None.

Study approval

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. All identifiable patient data have been anonymized.

Author contributions

MO: Writing, original draft creation. KZY: Writing, original draft creation. TN: Writing, original draft creation. MPC: Review and editing. MN: Review and editing.

Patient consent

Informed, written consent was received from all patients for whom photographs are present in the manuscript.