More Non-infectious Granulomatous Diseases! Karolyn Wanat, MD Assistant Professor, Dermatology & Pathology University of Iowa

Conflicts of Interest/Disclosure None

Classification/Overview 1) Necrobiotic/Palisading Blue collagenolyltic Red collagenolytic 2) Epithelioid Sarcoidal Tuberculoid 3) Foreign Body Endogenous Exogenous 4) Suppurative Infections Ruptured follicles/cysts Pyoderma gangrenosum 5) MISCELLANEOUS!

Necrobiotic/Collagenolytic Granulomas Blue Granuloma annulare Rheumatoid vasculitis Granulomatosis with polyangitis Red/Pink Necrobiosis lipoidica Rheumatoid nodule Necrobiotic xanthogranuloma Eosinophilic granulomatosis with polyangitis Eosinophilic cellulitis

Necrobiosis Lipoidica Wanat KA, Rosenbach M. UpToDate 2016.

NL: Clinical Usually bilateral, pretibial, lower extremities 15% involve trunk, upper extremities 1/3 ulcerate

NL: Path Diffuse palisaded and interstitial granulomatous dermatitis with layered inflammation parallel to skin surface Collagen alteration - pink Lymphoplasmacytic inflammation

Diabetes? Associations Found in <1% of diabetics Glycemic control not linked 1/3 patients with NL will develop DM Presence of NL may indicate higher risk of end-organ damage (proteinuria, retinopathy) Recalcitrant to treatment More likely to develop ulceration? Wanat KA, Rosenbach M. UpToDate 2016.

Reported Associations Thyroid disease Crohns Ulcerative Colitis Granuloma annulare Sarcoidosis Uveitis? Vascular disease? Wanat KA, Rosenbach M. UpToDate 2016.

Treatment HARD!!! Evidence lacking If non-ulcerated: active non-intervention is an option Monitor for squamous cell carcinoma

Avoid trauma to prevent ulceration Decrease edema: compression stockings Potent topical steroids under occlusion Intralesional steroids Topical tacrolimus Antimalarials Add pentoxifylline Add TCN antibiotics Phototherapy (PUVA>NBUVB) Other therapies reported: PDT, systemic steroids, TNF inhibitors (infliximab, adalimumab), cyclosporine, stanozolol, mycophenolate, fumuric acids, clofazamine fractional CO2 laser, excision Wanat KA, Rosenbach M. UpToDate 2014.

Ulcerated More aggressive multimodality therapy High potency topical corticosteroid or topical tacrolimus to the affected skin around the ulcer AND Topical PUVA, antimalarial, TCN antibiotic, or pentoxifylline UVA1, bovine collagen, mesha grafts, hyperbaric oxygen, intralesional infliximab, excision Wound care Wanat KA, Rosenbach M. UpToDate 2014.

Rheumatoid Nodules

RN: Clinical Subcutaneous nodules, frequently over bony prominences, especially around elbow and dorsal hands Nontender, round nodules, flesh-to-yellow, sometimes fibrotic and adherent to articular tissues

RN: Path Large focus of fibrin/necrobiosis with eosinophilic, altered collagen, surrounded by palisaded histiocytes Fibrosis over time

Associations Rheumatoid arthritis: 20-30% of patients SLE: 5% of patients Methotrexate induced accelerated nodulosis Can happen with other drugs

Treatment Challenging! Treat underlying rheumatoid arthritis Local therapy (injections) SSKI, dapsone, allopurinol Surgical excision

Necrobiotic Xanthogranuloma (NXG)

NXG: Clinical Indurated violaceous plaque with yellow hue, may have telangiectasia, atrophy, ulceration Periorbital is most common

www.visualdx.com

NXG: Path Palisading granulomas with necrobiosis around cholesterol clefts Presence of foamy histiocytes, giant cells Plasma cells Nodular lymphocytic inflammation Necrosis, neutrophils

Arch Dermatol. 2009;145(3):279-284

NXG: Associations! Paraproteinenia: 80% (IgG κ) 10% develop multiple myeloma Time to malignancy 8-11 years in some cases Other organs can be involved Ophthalmologic Heart Additional extracutaneous sites: lung, liver, spleen, myocardium, oropharynx, muscle, kidney, intestine, ovary

Work-up Laboratory studies: SPEP and immunofixation electrophoresis CBC CMP Lipid panel

Treatment Localized Surgical Excision Radiation IL steroids CO2 laser Systemic Systemic chemotherapy +/- prednisone Cyclophosphamide, melphalan, chlorambucil, interferonalpha 2a, methotrexate Thalidomide/lenalidomide + dexamethasone Plasmapheresis IVIG

Epithelioid Granulomas Sarcoidal Sarcoidosis Blau Foreign body Crohns disease Tuberculoid Tuberculosis Tuberculid Rosacea Perioral dermatitis Lupus miliaris disseminatum Crohns disease Other infections

Cutaneous Crohn s Disease

Cutaneous Crohn s: Clinical Non-specific/reactive Specific manifestations

Cutaneous Crohn s Non-Specific/Reactive Erythema nodosum Pyoderma gangrenosum Nutritional skin changes secondary to malabsorption Treatment-related manifestations

Cutaneous Crohn s Contiguous disease Specific Mucosal disease Distant metastatic disease

Specific Lesions Genital lesions > extragenital Genital edema (labial, scrotal): COMMON! Knife-cut ulcerations in the creases: specific Perianal ulcers, fissures, tracts, vegetating plaques Perianal skin tags (lymphatic obstruction) Oral mucosal cobblestoning, nodules, aphthae, ulcerations, pyostomatitis Metastatic: dusky erythematous plaques ulceration with undermined edges, draining sinuses and fistulas, and scarring

Cutaneous Crohn : Path Nodular non-caseating epithelioid granulomas with surrounding lymphocytes in the dermis and sometimes fat Granulomatous perivasculitis Ulceration +/- Sinus tracts, fistulas +/-

Treatment Treat most problematic system If active Crohns disease, coordinate with GI If controlled GI disease, consider: Topical, intralesional steroids Systemic steroids Metronidazole TNF inhibitors, azathioprine, cyclosporine Wound care if open lesions

J Am Acad Dermatol. 2014 Oct;71(4):804-13.

THANK YOU! Questions? karolyn-wanat@uiowa.edu

The Dermatology Foundation has supported & advanced my career.