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January 04, 2017

IgG4-Related Disease With Orbital Pseudotumors Treated With Rituximab Combined With Palpebral Surgery

Author Affiliations
  • 1Department of Dermatology, Assistance Publique-Hôpitaux de Paris (APHP), Saint-Louis Hospital, Paris VII Denis Diderot University, Paris, France
  • 2Department of Ophthalmology, Fondation Ophtalmologique A. de Rothschild, Paris, France
JAMA Dermatol. Published online January 4, 2017. doi:10.1001/jamadermatol.2016.4854

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder featuring tumefactions and a characteristic pathological pattern. We report a case of intermittent eyelid tumefactions that led to the diagnosis of IgG4-RD 6 years after initial presentation.

Report of a Case

A 51-year-old woman was admitted to the hospital for asymmetrical eyelid tumefactions. Six years earlier, she had had episodes of pruriginous inflammatory edema of the eyelid associated with elevation of total IgE level (1819.2 µg/L) and polyclonal hypergammaglobulinemia (1.74 g/dL). Immunological tests for antinuclear antibodies (ANAs), anti–double-stranded DNA antibodies (anti-dsDNAs), antineutrophil cytoplasmic antibodies (ANCAs), anti-Ro/SSAs, anti-La/SSBs, and complement activity produced negative results. Magnetic resonance imaging revealed periocular infiltration of the superior eyelids, including the lacrimal glands. Eyelid biopsy demonstrated a perivascular and interstitial infiltrate composed of polynuclear eosinophils and neutrophils that lacked features of lymphoma, lupus, or panniculitis. An accessory salivary gland biopsy excluded Sjögren syndrome or sarcoidosis. The diagnosis was chronic spontaneous urticaria with angioedema.

By the time of admission, the eyelid edema had become permanent and progressively became rock hard to palpation, which severely limited vision (Figure 1A). Levels of IgG1, IgG2, and IgG4 were elevated (IgG4, 202.53 mg/dL). A biopsy of the eyelid revealed a storiform-type fibrosis, with a dense inflammatory infiltrate composed of plasma and eosinophil cells around vessels without obliterative phlebitis (Figure 2A). Most plasma cells expressed IgG, with an IgG4/IgG ratio greater than 60%, and 116 IgG4-positive plasma cells counted per high-power field (Figure 2B). The findings led to the diagnosis of eosinophilic angiocentric sclerosis related to IgG4. Chest, abdomen, and pelvis computed tomography and positron emission tomography ruled out extraocular manifestations.

Figure 1.
Clinical Images of Bilateral Pseudotumoral Eyelid Tumefactions
Clinical Images of Bilateral Pseudotumoral Eyelid Tumefactions

A, Before rituximab infusions. B, Normal appearance of the eyelids 12 months after palpebral surgery and rituximab therapy.

Figure 2.
Biopsy Specimens From the Eyelid
Biopsy Specimens From the Eyelid

A, Storiform fibrosis with lymphoblastic and eosinophilic infiltrate (original magnification ×40). B, IgG4 positivity with IgG4+/IgG+ plasma cell ratio greater than 60% (original magnification ×10).

Treatment with prednisolone was administered (0.6 mg/kg/d for 6 weeks, followed by a 6-month tapering schedule) without any improvement. Then B-cell depletion therapy was started (rituximab, 1 g, 2 weeks apart). After 5 months, the intermittent inflammatory flares disappeared, and the edema greatly improved. The IgG4 level was 163.6 mg/dL (vs 231 mg/dL before treatment), and CD19+CD20-CD27+CD38bright plasmablast level was 650/mL (vs pretreatment level of 4523/mL). Nevertheless, the rock-hard fibrosis of the eyelid that limited vision persisted. The eyelid sclerosis was then removed surgically followed by 2 series of rituximab treatments every 6 months. One year later, there was complete softening of the eyelid tissues without recurrence of edematous flare, which allowed for satisfactory vision (Figure 1B).


The classic cutaneous presentation of IgG4-RD is pseudotumors, but cases of infiltrated plaques have also been described.1,2 Isolated skin involvement, such as in the present patient, is rare. Involvement of other organs should be investigated because IgG4-RD is linked to organ failure. The diagnosis is based on the presence of 2 of the following 3 pathological criteria: dense lymphoblastic infiltrates, storiform fibrosis, and/or obliterative phlebitis. On immunostaining, the IgG4+/IgG+ plasma cell ratio should exceed 40%, and more than 30 IgG4+ plasma cells per high-power field should be identified.3 In the present case, only the deep biopsy of the eyelid allowed identification of these pathological criteria, which were missed on the superficial biopsy.

Treatment is usually based on oral corticosteroid therapy.4,5 Rituximab, which can be useful for refractory or recurrent diseases,6 decreased circulating plasmablasts associated with the inflammatory activity. Nevertheless, the efficacy of rituximab for fibrosis is limited; therefore, when function is impaired surgery is indicated.5

This case report describes the treatment of eosinophilic angiocentric sclerosis related to IgG4 with isolated eyelid involvement that restored vision.

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Article Information

Corresponding Author: Manuelle Viguier, MD, PhD, Department of Dermatology, Saint-Louis Hospital, 1 Ave Claude-Vellefaux, 75475 Paris, CEDEX 10, France (mviguier@chu-reims.fr).

Published Online: January 4, 2017. doi:10.1001/jamadermatol.2016.4854

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information. We are also indebted to Claire Demongeot, MD, Maxime Battistella, MD, PhD, and Lionel Galicier, MD, for consultation and help in the management of this patient. These physicians received no compensation for their contributions.

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