Systemic Sarcoidosis After Polycaprolactone Fillers Successfully Treated with Upadacitinib

Dermal fillers are widely used in aesthetic medicine but may occasionally induce granulomatous reactions. We describe a case of systemic sarcoidosis developing after polycaprolactone filler injections, successfully treated with upadacitinib.

CASE PRESENTATION

A 56-year-old woman presented with progressive subcutaneous nodules in the nasolabial folds, chin and jawline that appeared 2 years after aesthetic filler injections with polycaprolactone (Ellansé®; polycaprolactone plus carboxymethylcellulose) in these areas. She reported no weight loss or systemic symptoms before or after the injections. Clinical examination revealed multiple subcutaneous nodules at the injection sites (Fig. 1A–B). An initial skin biopsy, performed shortly after presentation, demonstrated a foreign body granulomatous reaction consistent with filler-related inflammation (Fig. 1C). Methotrexate 10 mg weekly was discontinued due to adverse events, while intralesional and systemic corticosteroids yielded no clinical improvement.

Fig. 1. Clinical, histological and imaging findings at baseline.

(A–B) Subcutaneous nodules at the polycaprolactone filler (Ellansé®) injection sites in the nasolabial folds, chin and jawline. (C) Histopathological features of the initial biopsy showing residual foreign body material (yellow arrow) surrounded by a foreign body granulomatous reaction (green arrow), consistent with filler-related inflammation. (D) Repeat biopsy performed several months later revealing well-formed non-caseating granulomas composed of multinucleated giant cells and epithelioid histiocytes (orange arrows), compatible with sarcoidosis. (E) Baseline whole-body [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) demonstrating hypermetabolic supra- and infra-diaphragmatic lymphadenopathy (red arrows) together with pulmonary involvement, consistent with systemic sarcoidosis. Hypermetabolic subcutaneous facial nodules are also visible at the filler injection sites (blue arrows).

Given the persistence and progression of lesions, a second biopsy, performed several months later, showed non-caseating sarcoidal granulomas, consistent with sarcoidosis developing on foreign body material (Fig. 1D). Whole-body [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) demonstrated hypermetabolic supra- and infra-diaphragmatic lymphadenopathy and pulmonary involvement (Fig. 1E), consistent with systemic sarcoidosis. Hypermetabolic facial subcutaneous nodules were observed at the previously described injection sites. Given the refractory course and systemic involvement, upadacitinib 30 mg daily was initiated. After 6 months, cutaneous lesions markedly improved (Fig. 2A–B), together with a complete metabolic response on [¹⁸F]FDG PET/CT (Fig. 2C). Only slight residual metabolic activity persisted in small subcutaneous nodules along the mandibular ramus. No treatment-related adverse events were reported. At the 18-month follow-up, complete remission persisted (Fig. 2D–E).

Fig. 2. Clinical and imaging response to upadacitinib.

(A–B) Marked improvement of the cutaneous lesions 6 months after initiation of upadacitinib 30 mg daily. (C) Whole-body [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) after 6 months showing complete metabolic response of the supra- and infra-diaphragmatic lymphadenopathy and pulmonary involvement, with only slight residual metabolic activity in small subcutaneous nodules along the mandibular ramus. (D–E) Complete clinical remission after 18 months of continuous upadacitinib treatment.

DISCUSSION

Dermal fillers may act as adjuvants triggering immune activation. Unlike hyaluronic acid fillers, which are rapidly biodegraded and generally resorbed within months, polycaprolactone undergoes slow hydrolytic degradation over 2 to 4 years, potentially promoting prolonged immune stimulation and granuloma formation (1–3). Two hypotheses were considered in the present case: pre-existing, previously undiagnosed systemic sarcoidosis unmasked at the injection sites, or filler-induced cutaneous sarcoidosis with secondary systemic involvement. The absence of symptoms before the injections, the initially localized lesions, and the histological shift from a foreign body granuloma to a sarcoidal granuloma supported the second hypothesis (3, 4). However, the absence of prior chest imaging prevented a definitive conclusion.

While foreign body granulomas are well-recognized complications of dermal fillers, progression to systemic sarcoidosis remains exceptional (5–7). To the best of our knowledge, this is the first reported case of filler-associated systemic sarcoidosis successfully treated with upadacitinib. This finding aligns with evidence supporting Janus kinase (JAK) inhibitors in cutaneous and systemic sarcoidosis through modulation of the JAK-Signal transducer and activator of transcription (STAT) pathway, a key driver of granulomatous inflammation (5, 8). Favourable responses to upadacitinib in other granulomatous disorders, including granuloma annulare and granulomatous cheilitis, further support its therapeutic potential (9, 10).

This case underscores the importance of pharmacovigilance in aesthetic procedures, particularly regarding systemic granulomatous complications following dermal filler injections, and highlights the therapeutic potential of upadacitinib in sarcoidosis.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics committee

Informed consent for publication was obtained from the patient.

Disclosure

The data that support the findings of this case report are available from the corresponding author upon reasonable request