BSD Self Assessment Workshop 7 th July 2013 CASE 27 RAC6123
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1 BSD Self Assessment Workshop 7 th July 2013 CASE 27 RAC6123
2 M55. 4/7 tender lesions on knee, legs and arms. Also iritis/ weight loss/headache, synovitis.?vasculitis. Sarcoidosis. Biopsy from left elbow
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5 Churg Strauss granuloma
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9 Differential Diagnosis for BSD Workshop A. Granuloma annulare B. Rheumatoid nodule C. Rheumatic fever D. Sweet's syndrome E. Palisaded neutrophilic and granulomatous dermatitis
10 A and B) Interstitial granulomatous dermatitis with focally prominent neutrophils and moderately numerous eosinophils. Histology has a close resemblance to granuloma annulare including prominent mucin. This reaction pattern is commonly associated with underlying systemic disorders including vasculitides, other autoimmune disorders and viral infection. from SpR: Patient being treated now with methotrexate for synovitis, iritis, skin rash, Dr XXX has diagnosed Sweet's syndrome presenting similarly to vasculitis. RAC Comment: Histology is NOT typical of Sweet s that can have a late granulomatous phase but does not have interstitial granulomatous pattern or Churg Strauss type granulomas (not to be confused with Churg Strauss syndrome). Clinico-Pathologic Diagnosis Palisaded neutrophilic and granulomatous dermatitis (PNGD) (AKA interstitial granulomatous dermatitis with arthritis, IGDA)
11 Palisading Neutrophilic granulomatous dermatitis (PNGD) Uncommon dermatological disorder commonly associated with synovitis Usually presents in middle age More common in women Associated with underlying autoimmune disease eg. Rheumatoid arthritis, vasculitis Thought to be secondary to a vasculitic process No reports of eye involvement Treatment-as per vasculitis
12 PNGD: Histology Intense neutrophilic infiltrate and nuclear dust Interstitial histiocytic infiltrate Collagen degeneration There may also be leukocytoclastic vasculitis Variable histological appearance depending on stage of the eruption Palisading granulomas seen have also been described as miniature Churg-Strauss granulomas or flame figures, with degenerated collagen enveloped by eosinophils resembling a flame On a spectrum with interstitial granulomatous dermatitis
13 Interstitial Granulomatous Dermatitis (with Arthritis) Ackerman AB, et al. Clues to Diagnosis in Dermatopathology. American Society for Clinical Pathology Press, Chicago. 1993:309 Heterogeneous entity Red or skin-coloured patches, papules and/or plaques Round, annular or cord-like (Rope Sign) Wax and wane Usually symptomless Symmetrically distributed, trunk +/- proximal limbs > in middle-aged women Arthritis may occur prior to, concurrent with, or after the cutaneous presentation Arthritis is typically thought to be non-erosive and not deforming although this is not universally the case.
14 Example Clinical Images from Internet Removed from Presentation
15 c/o Dr Eduardo Calonje Rope Sign subcutaneous linear cords that were thought to be pathognomonic Clinical Image removed from Presentation Ackerman AB, et al. Clues to Diagnosis in Dermatopathology. American Society for Clinical Pathology Press, Chicago. 1993:309
16 Associations of IGDA (and PNGD) AUTOIMMUNITY Rheumatoid arthritis Systemic lupus erythematosus Primary antiphospholipid syndrome Autoimmune thyroiditis Autoimmune hepatitis MISCELLANEOUS Pulmonary silicosis Acute promyelocytic leukemia Chronic uveitis Paraneoplastic in association with bronchial SqCa INFECTIONS HIV Parvovirus B19 Lyme disease Hepatitis C EBV Mycoplasma Molluscum contagiosum Pulmonary coccidioidomycosis AETIOLOGY Probable immune complex deposition
17 Histopathology of IGDA Dense histiocytic inflammation in reticular (lower) dermis Fewer numbers of neutrophils and eosinophils (c/w PNGD +/-Perivascular and interstitial lymphocytes Histiocytes are mostly interstitial (between collagen bundles) or palisaded around collagen (lined up perpendicular to the central fragmented collagen) Focal degeneration of collagen may be surrounded by empty space (floating sign) Giant cells are uncommon +/- Leucocytoclastic vasculitis IMF: C3, IgM, fibrinogen +/- Mucin (usually < than GA)
18 Rope Sign Clinical Image removed from Presentation c/o Dr Eduardo Calonje
19 c/o Dr Eduardo Calonje
20 Some Serological Abnormalities in IGDA Rheumatoid factor (RhF) Antinuclear factor (ANA) Thyroglobulin SS-A Histone DNA histone ANCA Verneuil et al Interstitial granulomatous dermatitis with cutaneous cords and arthritis: A disorder associated with autoantibodies. J Am Acad Dermatol 2001;45:286-91
21 Treatment & Course of IGDA Treatments for IGDA are not well defined Resolution of IGDA has been documented after treatment with systemic glucocorticoids, topical glucocorticoids, systemic and topical glucocorticoids together, nonsteroidal antiinflammatory agents and topical glucocorticoids together, and infliximab Spontaneous resolution and treatment resistant forms have been described
22 Differential Diagnosis for BSD Workshop A. Granuloma annulare More often extremities c/w trunk in IGD Less often associated with autoimmuned disease Upper dermis, blue (mucin) granulomas Rare or absent neutrophils & eosinophils B. Rheumatoid nodule C. Rheumatic fever D. Sweet's syndrome E. Palisaded neutrophilic and granulomatous dermatitis
23 Granuloma Annulare Classical Clinical Image removed from Presentation RAC4102
24 RAC4102
25 RAC4102
26 RAC4728
27 RAC2499
28 RAC2499
29 RAC2499
30 Granuloma Annulare Interstitial / Incomplete RAC2819
31 RAC2819
32 RAC2819
33 RAC2819
34 Differential Diagnosis for BSD Workshop A. Granuloma annulare B. Rheumatoid nodule Association with rheumatoid arthritis Red (fibrin) granulomas C. Rheumatic fever D. Sweet's syndrome E. Palisaded neutrophilic and granulomatous dermatitis
35 Rheumatoid nodule RAC3538
36 RAC3538
37 RAC3538
38 Granuloma Annulare (rheumatoid nodule like) RAC4314
39 RAC4314
40 Alcian Blue (stromal mucin) RAC4314
41 Differential Diagnosis for BSD Workshop A. Granuloma annulare B. Rheumatoid nodule C. Rheumatic fever D. Sweet's syndrome E. Palisaded neutrophilic and granulomatous dermatitis
42 Rheumatic Fever Histology similar to PNGD
43 Differential Diagnosis for BSD Workshop A. Granuloma annulare B. Rheumatoid nodule C. Rheumatic fever D. Sweet's syndrome E. Palisaded neutrophilic and granulomatous dermatitis
44 Sweet s syndrome Uncommon Associated with malignancy, underlying autoimmune disease, often triggerred by upper respiratory tract infection Can be associated with eye and joint involvement Eye and joint involvement less commonly seen in Sweet s syndrome secondary to underlying malignancy Early histology neutrophilic dermatosis with leucocytoclasis Late histology histiocytic / granulomatous reaction with residual leucocytoclasis
45 Don t forget drug reactions
46 84. Asymptomatic eruption eight months. Upper back and arms RAC2841
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52 Histology Summary Epidermis is normal Histiocytes and lymphocytes in an interstitial distribution - in the superficial and upper reticular dermis Perivascular lymphocytes and plasma cells present
53 CD68
54 Diagnosis Interstitial Granulomatous drug reaction or Incomplete (Interstitial) Granuloma Annulare Superficial infiltrate and absence of collagen necrobiosis supports IGDR
55 Drugs implicated Calcium channel blockers Beta blockers ACE inhibitors Lipid lowering agents Antihistamines Anticonvulsants Antidepressants Combination of a thiazide diuretic and HRT
56 Further Clinical Information PMH - Hypertension and gout. Enalapril Fortipine Fluvastatin Omeprazole, allopurinol and diclofenac Fluvastatin was withdrawn Gradual resolution of eruption in the subsequent six months
57 Interstitial Granulomatous Drug Reaction 20 cases reported in 1998 Erythematous / Violaceous plaques Annular Non-pruritic Isolated or widespread Arms, medial thighs, intertriginous areas, trunk Magro et al J Cutaneous Path 1998
58 Histology: IGDR Resembles incomplete form of GA Superficial dermis-hypercellular Interstitial infiltrate - lymphocytes and histiocytes. +/- Piece-meal fragmentation of collagen and elastic fibres with elastophagocytosis. +/- Interface dermatitis/epidermotropism +/- multinucleate giant cells +/- Eosinophils - small numbers Neutrophils absent 50% have atypia of lymphoid infiltrate
59 DRUG REACTIONS ARE USUALLY NOT SUSPECTED Patients are often on more than one drug Lesions resolve on cessation of drug
60 Interstitial Granulomatous Drug In IGDR Reaction Differs from GA absence of significant necrobiosis predominance of lymphocytes over histiocytes presence of eosinophils interface change.
61 Granulomatous CTCL Should be considered if there is more extensive lymphoid atypia Or if the lesions do not resolve after drug modulation (repeat biopsies/molecular studies)
62 Take Home Messages IGDA & PNGD represent a reaction patterns that may be seen in many conditions including autoimmune disease, infections and as a type of drug eruption Histological spectrum that overlaps with rheumatic fever nodules, granuloma annulare, Churg-Strauss granuloma, necrobiosis lipoidica and interstitial granulomatous drug reactions Thank You!
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