A Case of IgG4-Related Disease with Cutaneous Manifestations

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1 A Case of IgG4-Related Disease with Cutaneous Manifestations Ashley E. Sutherland 1, Peter J. Green 1, and Thai Yen Ly 2 Division of Clinical Dermatology and Cutaneous Science 1 and Department of Pathology 2 Dalhousie University, Halifax, NS, Canada Learning Objectives: 1. Recognize the cutaneous manifestations associated with IgG4 related disease and what visceral manifestations should be considered. 2. Understand investigations and work-up required for confirmation and investigation of IgG4 related disease. 3. Review management and treatment options for IgG4 related disease. Take Away Message: IgG4 related disease is a recently recognized clinical syndrome associated with increased serum IgG4 levels and chronic fibroinflammatory changes in a number of organ systems. Cutaneous manifestations may include infiltrated papulonodules typically seen on the face and neck however, cutaneous findings vary considerably. While visceral involvement is protean, more classic association includes salivary and lacrimal gland infiltration, lymphadenopathy and autoimmune pancreatitis. Patients tend to respond well to oral corticosteroids however other immunosuppressive therapies have also been used. This entity is a relatively newly recognized condition that dermatologists may encounter; early recognition to confirm diagnosis and reduce potential morbidity highlight a dermatologists potential role in patient care. Conflict of Interest: We have no conflicts to declare. Contact Information:

2 Introduction IgG4 related disease (IgG4-RD) is a recently recognized syndrome characterized by cutaneous and systemic tissue infiltration of IgG4-positive plasma cells and chronic fibroinflammatory change affecting many organ systems. Often, but not always, serum IgG4 levels are also elevated. Most commonly, patients manifest salivary and lacrimal gland swelling, lymphadenopathy and autoimmune pancreatitis. We present a case of a 61 year old male with a 10 year history of multiple chronic symptoms including diffuse lymphadenopathy and skin disease that histology ultimately confirmed to be consistent with IgG4-RD History of Illness The patient s clinical presentation occurred over a decade and included various symptoms including diffuse lymphadenopathy with salivary gland involvement along with left submandibular sialadenitis. Skin disease initially presented as diffuse itch and was histologically diagnosed as lichenoid dermatitis on the extremities and face (Figure 1, Figure 2). This progressed to infiltrated pruritic papulonodules on the arms, buttocks, neck and face. Subsequent skin biopsy demonstrated a nodular, moderately dense and predominantly deep mixed cell lymphoproliferative infiltrate (Figure 3) suggestive of pseudolymphoma or lymphomatoid papulosis.

3 History of Illness The patient s clinical presentation occurred over a decade and included various symptoms including diffuse lymphadenopathy with salivary gland involvement along with left submandibular sialadenitis. Skin disease initially presented as diffuse itch and was histologically diagnosed as lichenoid dermatitis on the extremities and face (Figure 1). This progressed to infiltrated pruritic papulonodules on the arms, buttocks, neck and face. Subsequent skin biopsy demonstrated a nodular, moderately dense and predominantly deep mixed cell lymphoproliferative infiltrate (Figure 2) suggestive of pseudolymphoma or lymphomatoid papulosis. A B C Figure 2. A. Infiltrated pruritic papulonodules on the face along with chronic, persistent cervical lymphadenopathy B. Infiltrated pruritic papulonodules on the extensor arm initially diagnosed as pseudolymphoma and C. Pruritic papules on the buttock diagnosed as lichenoid dermatitis.

4 Diagnosis A recent right scalene lymph node excisional biopsy noted IgG4-positive staining of plasma cells which was confirmed retrospectively on review of previous skin biopsies as well in conjunction with typical histologic findings for IgG4-RD (Figure 2). Serum IgG4 was found to be elevated at 1.931g/L (normal range g/L). Total IgG was 10.20g/L (normal g/L). Screening magnetic resonance imagine of the abdomen showed chronic dilatation of the pancreatic duct without obvious fibrosis or stricturing suggestive of active IgG4-RD. Recent CT scan of the thorax showed persistent, unchanged axillary lymphadenopathy. A B C Figure 2. A. Skin biopsy of extensor arm on low power showing a nodular and cellular infiltrate in the deep dermis and subcutis. B. High power showing infiltrate is composed of plasma cells, lymphocytes and eosinophils. C. IgG4+ plasma cells within skin lesion.

5 Discussion Chronic fibroinflammatory change in many organ systems, including the skin, is commonly seen in IgG4-RD. Histology specimens typically demonstrate a dense lymphoplasmacytic infiltrate organized in a storiform pattern with obliterative phlebitis and a mild to moderate eosinophil infiltrate. As well, immunohistochemical staining confirms IgG4+ plasma cells. When compared to total IgG+ cells, ratio of IgG4:IgG positivity of greater than 50% is supportive of the diagnosis. Diagnostic Criteria for IgG4-RD 1. Diffuse or localized swelling or masses in a single or multiple organs on physician exam 2. Elevated serum IgG4 concentration ( 135mg/dL) 3. Histopathology showing a. Marked lymphocyte and plasma cell infiltration b. Fibrosis and infiltration of IgG4+ plasma cell with a ratio of IgG4:IgG of >40% and greater than 10 IgG4+ plasma cells per HPF Treatment Patients may respond well to systemic or topical corticosteroids however other immunosuppressive therapies have also been used on occasion such as rituximab, azathioprine and methotrexate.

6 Conclusion IgG4-RD is a relatively newly recognized condition with involvement of multiple organ systems, including the skin, that dermatologists must be aware of as the clinical presentation can mimic a number of other conditions and delay proper diagnosis and treatment. References Stone J.H., Zen Y. and V. Deshpande. IgG4-Related Disease. New England Journal of Medicine 2012; 366(6): Charrow A., Imadojemu S., Stephen S., et al. Cutaneous Manifestations of IgG4-related disease (RD): A systematic review. J Am Acad Dermatol 2006; doi: /j.jaad

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