A 19-year-old man presented at Month 0 with a two-month history of rapidly progressive skin tightening and hyperpigmentation on his left lower leg. The initial lesion, which appeared approximately two months prior to presentation on the lateral aspect of the left calf, was characterized by indurated, hyperpigmented skin with localized atrophy. It quickly spread distally to involve the dorsum of the left foot and the third and fourth toes, leading to mild restriction of left foot flexion and extension. The patient’s past medical history was unremarkable aside from allergic rhinitis. He denied any systemic symptoms suggestive of systemic sclerosis (SSc) – such as fever, Raynaud’s phenomenon, arthritis, myalgias, dysphagia, or any signs of internal organ involvement. There was no sclerodactyly or nailfold capillary abnormality.

On physical examination, the affected skin over the left lateral lower leg, the dorsum of the left foot, and the third and fourth toes was firm, swollen, hyperpigmented, and showed areas of local depression consistent with atrophy, following a linear band-like distribution (Figures 1A, B).

Routine laboratory tests, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin levels, and hepatic/renal function, were all within normal limits. Crucially, the Antinuclear Antibody (ANA) test was negative, helping to differentiate the condition from SSc. Anti-topoisomerase I (Scl-70) and anticentromere antibodies were also negative.

Comprehensive serological evaluation revealed the presence of multiple aPLs. The patient tested positive for lupus anticoagulant (LA; dilute Russell viper venom time ratio 1.34) and had elevated anti-phosphatidylserine/prothrombin IgM (143.72 U), β2-glycoprotein I IgM (30.9 CU), and anticardiolipin IgM (28.2 CU). Although he did not meet the full clinical criteria for antiphospholipid syndrome (APS) (e.g., no thrombotic events or pregnancy morbidity), this profile indicated a state of significant autoimmune-mediated vascular activation. He had no clinical features suggestive of systemic lupus erythematosus and did not fulfill classification criteria for SLE.

Given the aggressive, rapidly progressive nature of the disease and the involvement of deep structures (with high risk for permanent damage), an early intensified multi-target combination therapy was initiated at baseline (Month 0): No concomitant topical therapy was used. A schematic timeline of the treatment course and responses is provided in Figure 4.

Deep morphea (morphea profunda) is characterized by inflammation and sclerosis extending into the deep dermis, subcutaneous fat, and sometimes the underlying fascia or muscle. This subtype of LoS is associated with significant morbidity, particularly when it affects the extremities, as it can cause joint contractures, muscle atrophy, and permanent functional deficits (13). In our patient, the diagnosis of deep morphea was firmly established by histopathology and, critically, by baseline MRI, which demonstrated inflammatory edema tracking along the fat lobules and muscle septa (14). The use of advanced imaging techniques is crucial for deep variants of LoS. MRI, in particular, is highly effective for visualizing the full extent of tissue involvement and detecting active inflammation (edema and contrast enhancement), thereby aiding in both initial assessment and monitoring of treatment response (15). In this case, a 6-month follow-up MRI showing marked reduction of subcutaneous edema provided objective evidence that the therapeutic intervention successfully suppressed the deep inflammatory process. Although eosinophilic fasciitis can show fascial signal abnormalities on MRI, it typically demonstrates more diffuse and symmetric fascial thickening and enhancement (16); this pattern was not observed in our patient, and peripheral eosinophilia was absent.

Current therapeutic consensus recommends systemic MTX (often combined with corticosteroids) as first-line treatment for aggressive or high-risk LoS, in order to halt disease progression and prevent irreversible damage (6, 7). However, the efficacy of these conventional therapies in severe, deep-seated adult morphea is variable and often suboptimal. In our patient, the combination of rapid progression, deep tissue involvement, and impending functional impairment justified immediate escalation to targeted biologic therapy rather than awaiting failure of MTX alone. This approach aligns with a “treat-to-target” philosophy, aiming to aggressively quench the active inflammation and fibrotic cascade before irreversible fibrosis occurs. Based on this experience, early TCZ may be considered in patients with rapid disease progression, objective evidence of deep inflammatory activity on MRI, and/or imminent risk of functional impairment.

IL-6 plays an integral role in LoS pathogenesis by promoting fibroblast activation and collagen deposition (17–19). TCZ interrupts this pathway by blocking IL-6 signaling. While TCZ has predominantly been reported in severe or refractory cases of LoS (especially in pediatric patients who failed multiple immunosuppressants) (11, 12), our case demonstrates the benefit of integrating TCZ early in the treatment course. Using such a potent agent during the active inflammatory phase likely contributed to the swift remission, supporting the idea that timely intervention with targeted therapy can prevent the progression to crippling fibrosis. Indeed, the successful outcome in this case suggests that TCZ can be a justifiable first-line adjunct in selected aggressive cases of adult deep morphea, representing a potential advance in clinical practice. Notably, both radiological improvement and clear clinical softening were evident by 6 months, whereas most published TCZ cases were treated after prolonged refractory disease (11, 12, 20–23). Nevertheless, intensive combination therapy should be individualized and closely monitored, and it should not be interpreted as universally applicable to all cases of deep morphea.

To date, approximately 26 cases of localized scleroderma treated with TCZ have been reported in the literature, nearly all as salvage therapy after failure of MTX and other immunosuppressives. These reported cases have occurred predominantly in pediatric patients (11, 20–23), most of whom had long-standing, severe disease (often linear, generalized, or pansclerotic subtypes) with extracutaneous or even neurologic/ocular involvement (24, 25), and TCZ was usually added on top of MTX or MMF as rescue therapy, leading to at least partial clinical improvement in the great majority of cases (Table 1). In contrast, only a few adult patients with refractory generalized or pansclerotic morphea have been described (9, 10, 24), again receiving TCZ late in the disease course as second- or third-line treatment. Taken together, the cases summarized in Table 1 indicate that TCZ has mainly been used as a “last-resort” option in deeply fibrosing, treatment-resistant morphea. Notably, our patient is one of the first adults with deep morphea to receive TCZ as an early-line component of combination therapy, and his case is further distinguished by the unique coexistence of multiple aPL positivity. Other biologics (e.g., abatacept and rituximab) and emerging targeted therapies have also been reported for severe/refractory LoS, but evidence remains limited (18, 19).

The co-occurrence of LoS with multiple positive aPLs in this patient is an exceptionally rare finding (26, 27). LoS is generally not associated with the systemic microvascular pathology seen in SSc; however, the presence of aPLs denotes a prothrombotic and vasculopathic state. It is conceivable that the aggressive nature of our patient’s morphea was exacerbated – or at least influenced – by an underlying vascular insult mediated by these autoantibodies (28). This consideration influenced our management: we incorporated low-dose aspirin as a preventative measure against thrombotic events (7), given the significant aPL profile. Such an approach (combining immunosuppression with vascular prophylaxis) is uncommon in LoS and highlights the importance of tailoring therapy to individual patient risk factors.

This case underlines the need for thorough serological evaluation in severe or atypical presentations of localized scleroderma. In patients with unusually aggressive disease courses or features suggestive of systemic involvement, screening for concurrent autoimmune markers (e.g., aPLs) may uncover overlaps that have implications for both prognosis and treatment. Identifying an aPL overlap in our patient guided the addition of antithrombotic prophylaxis and alerts clinicians to monitor for potential vascular complications. More broadly, recognizing such overlaps can facilitate a multidisciplinary management approach and inform prognosis, as patients with concurrent autoimmune phenomena might warrant closer follow-up.