Bullous periorbital oedema in anti-p155/140-positive dermatomyositis: a case series

Dear Editor, Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by immune-mediated skin and muscle injury. There is a diverse spectrum of clinical phenotypes within DM, and this clinical heterogeneity can challenge timely recognition and diagnosis [1].

Myositis-specific antibodies are increasingly utilized to facilitate recognition of DM subgroups, and provide important insights into clinical phenotypes, prognosis and treatment response [1–3]. Anti-p155/140 (TIF-1γ) antibody is associated with increased malignancy risk, refractory disease and distinct cutaneous lesions [e.g. verruca-like palmar papules, hypopigmented and telangiectatic (‘red on white’) patches, and an erythematous ovoid palatal patch] [3, 4]. Herein, we describe five cases of DM with bullous periorbital oedema identified at the Johns Hopkins Myositis Center, all of whom were positive for anti-p155/140, suggesting that this may represent a novel clinical manifestation of this subgroup.

Case 1

A 76-year-old white female presented with a 6-month history of periorbital oedema, proximal muscle weakness and dysphagia (Supplementary Table S1, available at Rheumatology online). Bullous periorbital oedema with heliotrope rash (Fig. 1A), non-scarring alopecia and proximal muscle weakness were noted. Creatinine kinase (CK) was mildly elevated (303 U/l: upper limit of normal 182 U/l). Aldolase was normal (7.9 U/l: upper limit of normal 8.1 U/l). Anti-p155/140 was positive. EMG showed non-irritable myopathy, while MRI noted extensive intramuscular and fascial oedema involving the pelvic and thigh muscles. Bullous oedema and weakness resolved with glucocorticoids, MTX and IVIG (Fig. 1B).

Case 2

A 61-year-old white female presented with a 15-month history of an erythematous rash affecting the face and chest, and an 8-month history of proximal muscle weakness and dysphagia. Examination noted diffuse facial erythema with marked bullous periorbital oedema (Fig. 1C), palmar macules and proximal muscle weakness. CK was mildly elevated (353 U/l); aldolase was normal (8 U/l). Anti-p155/140 antibody was positive. EMG noted a non-irritable myopathy. Muscle and fascial oedema were present on thigh MRI. She had progressive disease unresponsive to glucocorticoids, MTX and IVIG.

Case 3

A 60-year-old Black female presented with a 1-year history of bilateral periorbital oedema, erythematous rash involving the chest and face, and proximal muscle weakness. Additional symptoms included dysphagia and a recurrent oral ulcer. Bullous periorbital oedema with heliotrope rash (Fig. 1D) and proximal muscle weakness were noted. The severity of periorbital oedema prompted concern for angioedema. CK was normal (86 U/l). Aldolase was mildly elevated (9.1 U/l). Anti-p155/140 and anti-Ro60 antibodies were positive. EMG showed irritable myopathy, while thigh MRI showed oedema. She was treated with glucocorticoids, MMF and IVIG with excellent response in both cutaneous and muscular manifestations.

Case 4

A 45-year-old white female presented with a 17-month history of proximal muscle weakness, photosensitive rash and dysphagia. Gottron’s papules, V-sign, marked periorbital oedema (Fig. 1E) and proximal weakness were noted. There was concern for angioedema. CK and aldolase were elevated (840 U/l and 45 U/l respectively). Anti-p155/140 was positive. EMG showed irritable myopathy. MRI noted intramuscular and fascial oedema of the thighs. She was treated with glucocorticoids, MMF and IVIG. While muscle manifestations responded well, cutaneous manifestations remained refractory to multiple therapies including AZA, MTX, tacrolimus and rituximab. She was subsequently transitioned to tofacitinib in combination with glucocorticoids, with complete resolution of bullous oedema (Fig. 1F).

Case 5

A 64-year-old white female presented with a 5-month history of proximal upper extremity weakness and rash. Examination noted Gottron’s papules and erythematous periorbital oedema. She was treated with glucocorticoids and AA. One year later, she was evaluated at our centre where she endorsed ongoing symptoms with associated dysphagia. Examination noted bullous periorbital oedema (Fig. 1G) and neck flexor weakness. Muscle enzymes and EMG were normal. Anti-p155/140 antibody was positive. MRI demonstrated fascial oedema. She derived excellent response from MMF and IVIG.

Discussion

Herein, we describe five patients with anti-p155/140-positive DM in whom bullous periorbital oedema was a dominant clinical manifestation. Of note, the severity and bullous character of periorbital oedema prompted concern for angioedema in two participants. Other aetiologies to consider include IgG4-related disease, sarcoidosis and SS. To date, few reports of severe periorbital oedema in DM have been described; in these cases, DM was not considered until other more characteristic skin manifestations appeared [5, 6].

All five participants reported dysphagia, which portends poor prognosis [7], yet all except one responded to immunosuppressive therapy, highlighting the need for early recognition of this distinct, yet treatable subgroup. Oedematous myositis has previously been described as a relatively homogeneous phenotype characterized by severe myopathy, with pathophysiological implications of complement cascade and vasculopathy [8]; a similar mechanism may occur in the skin causing bullous periorbital oedema, but further studies are required. Of note, no participant developed malignancy over the course of follow-up.

Our findings suggest that bullous periorbital oedema may represent a unique clinical manifestation in a subset of anti-p155/140 DM. Unless clinicians are aware that bullous periorbital oedema is a treatable manifestation of DM, even in the absence of more characteristic cutaneous lesions, diagnosis may be delayed conferring poorer outcomes.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

The data that support the findings of this study are not publicly available due to privacy or ethical reasons.

Contribution statement

Substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work: C.M.C., L.X., M.A., L.C.-S., J.J.P. Drafting the work or revising it critically for important intellectual content: C.M.C., L.X., E.T., C.A.M., B.L.A., J.A., L.C.-S., J.J.P. Final approval of the version to be published: C.M.C., L.X., E.T., C.A.M., B.L.A., J.A., L.C.-S., J.J.P. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: C.M.C., L.X., E.T., C.A.M., B.L.A., J.A., L.C.-S., J.J.P.

Funding

This work was supported by the Jerome L. Greene Foundation Discovery Fund (C.M.C, J.J.P, E.T.), and grant numbers K23AR073927 (J.J.P.), K23AR075898 (C.A.M.) and K08AR077732 (E.T.) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Disclosure statement: J.J.P. reports consultant fees from Alexion, Riovant, ArgenX, EMD-Serono, Pfizer, Kezar, Guidepoint; and clinical trial research support from Alexion, Pfizer, Kezar. L.C.-S. reports consultant fees from Janssen, Boehringer-Ingelheim, Mallinckroft, EMD-Serono, Allogene and ArgenX. E.T. reports consulting fees from Horizon. The other authors of this manuscript have no relevant financial disclosures or conflicts of interest to disclose as described by Rheumatology.

Ethics: Informed consent has been obtained.

References

Author notes