58 yo woman referred for unresponsive drug rash
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1 12:50-1:50pm Can't Miss Dermatology Diagnoses: Cutaneous Manifestations of Systemic Disease SPEAKER Daniela Kroshinsky, MD MPH Disclosures The following relationships exist related to this presentation: Daniela Kroshinsky, MD MPH: No financial relationships to disclose. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Overview Identify cutaneous manifestations of systemic disease and their associated risk factors Review treatment options 58 yo woman referred for unresponsive drug rash Learn other mimicking cutaneous conditions
2 Dermatomyositis Ragged cuticles, nail fold telangiectasias Extensor limb rash, including knuckles Shawl distribution poikiloderma with extension into scalp Periorbital edema, heliotrope rash Diffuse facial erythema, malar erythema Holster sign More violaceous and pruritic than lupus Erosions, ulcerations
3 Forms Resembles polymyositis; symmetric proximal muscles usually Skin findings precede muscle in most cases Classic (with muscle disease) Amyopathic (myositis may evolve over time) Hypomyopathic dermatomyositis (no clinical muscle weakness, but myositis present on radiographic or laboratory testing) Other systems Pulmonary disease occurs in approximately 15 30% Generally presents as a diffuse interstitial fibrosis Cardiac disease is not commonly symptomatic Usually presents as arrhythmias or as conduction defects Malignancy Association Estimated 10% to over 50% of patients Genitourinary (esp ovarian) and colon malignancies may be overrepresented, nasopharyngeal in some SE Asian populations Common others: breast, lung, gastric, pancreatic, lymphomas (including non Hodgkin) The risk of malignancy may normalize after 2 5 y Frequent and thorough medical histories, repeated ROS, complete physical exams, and screening labs
4 Malignancy Screening Mimickers Urinalysis, stool occult blood testing Serum prostate specific antigen Serum CA125 Mammogram and transvaginal pelvic U/S CT of chest, abdomen and pelvis Colonoscopy if age appropriate, iron deficiency anemia, fecal occult blood, or symptoms Upper endoscopy if colonoscopy negative in the setting of iron deficiency anemia, fecal occult blood, or symptoms 31 yo W with anxiety, palpitations, and recurrent cellulitis
5 31yo W h/o bipolar disorder, anxiety, hypothyroidism and deep vein thrombosis on warfarin Presents to ED with anxiety, palpitations, and left calf edema, pain, and erythema Three weeks prior to presentation, she developed redness, pain and swelling of her left leg U/S negative, pelvic MRI negative Course of clindamycin Two weeks later, develops same symptoms on right leg, started on levofloxacin 500mg qd and furosemide with improvement by day 5 New left leg pain, swelling and erythema Chart Review 10/2013 had similar incident and was found to have L leg DVT in absence of immobility or smoking, + OCP which was discontinued Warfarin for 3 months and then stopped 4/2014 pt has similar episode and found to have L leg DVT Warfarin restarted Normal workup per patient
6 No personal or family h/o miscarriages, PE, clotting disorders ROS negative for weight loss, fatigue, malaise, fever, chills Afebrile, HR 128, SO2 100% on room air Concern for thrombophlebitis, DVT Repeat U/S, coagulopathy workup, ANA, dsdna, anti Ro and La, and anti Smith More detailed history: photosensitivity but no malar or discoid rash, arthritis, serositis, kidney disease, neurologic symptoms Pertinent Labs: WBC 3.7, Hct 35, ESR 85, INR 3 Course Hypercoagulability workup: 10/2013: Normal Factor V Leiden, Prothrombin gene mutation, Protein C & S levels 4/2014: +anticardiolipin Ab, lupus anticoagulant, beta 2 glycoprotein, normal antithrombin III U/S demonstrates left popliteal vein thrombosis Hematology increases INR goal to 3 4, monitor Repeat acl IgG 38 and B2GP ANA 1:5120, dsdna 1:80, Anti Sm and Anti RNP positive Diagnosis: Systemic Lupus Erythematosus with secondary : Antiphospholipid Antibody Syndrome Hydroxychloroquine 200 mg BID
7 Pseudocellulitis Dozens of clinical mimickers of cellulitis: pseudocellulitis, no gold standard diagnostic tool Estimated misdiagnosis rate as high as 30% Most common mimicker: stasis dermatitis Empiric use of aggressive antibiotics rising rates of resistance in soft tissue infections 98 04: MRSA soft tissue infections % Moet GJ et al. Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program ( ). Diagn Microbiol Infect Dis 2007;57:7 13. David, C.V., et al., Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online J Mar 15:17(3):1. 32 year old W admitted for diarrhea and weight loss with itchy plaques on the legs
8 Localized (Pretibial) Myxedema TSH <0.01, T4 = 25 Graves disease A/w hyperthyroidism (usually Graves), may appear w/ hypothyroidism that follows treatment Found in 1 5% of patients with Graves, but up to 25% of those with exophthalmos Rarely, in Hashimoto s thyroiditis without thyrotoxicosis, and euthyroid patients Rarely, face, shoulders, upper extremities, lower abdomen, scars or donor graft sites Cutaneous manifestations of hyperthyroidism Warm, moist skin, with increased temperature Diffuse non scarring alopecia Palmoplantar hyperhidrosis Facial flushing Increased skin pigmentation Onycholysis (aka Plummers nails) 56 yo M admitted for pancytopenia, found to have leg rash
9 DDx Pruritic Present for 6 weeks Noticed after leg scratched on a bush Not improved with triamcinolone cream Infectious Dermatophyte Subcutaneous mycoses (chromoblastomycosis) Atypical mycobacteria Less likely bacterial, sporothrix or systemic mycoses Inflammatory Contact dermatitis Eczema Reactive phenomena Diagnostic Studies KOH negative Tissue culture Gram stain (-) Culture grew CoNS Acid fast smear (-) Mycobacterial culture (-) Fungal culture (-) Punch biopsy
10 Necrolytic Acral Erythema Necrolytic Acral Erythema Type of necrolytic erythema Necrolytic Migratory Erythema (glucagonoma) Nutritional Deficiency (zinc/acrodermatitis enteropathica, niacin/pellagra, biotin, essential fatty acids) In chronic hepatitis, prevalence is 1.7% First described in 1996 Case series of 7 patients from Egypt with hepatitis C Patient s Hepatitis Viral Load: 748,000 Predilection for dorsal feet and lower extremities Treatment Oral zinc supplementation 440 mg/day, divided BID Hepatitis C treatment Topical corticosteroids are NOT effective Necrolytic Migratory Erythema Glucagonoma Analogous to acrodermatitis enteropathica HCV & Lichen Planus Up to 38% of patients with LP, especially associated with oral form Inquire esophageal ROS, genital involvement Nejm.org Dermnz.net
11 Necrobiosis Lipoidica Diabeticorum Necrobiosis Lipoidica Diabeticorum Associated with diabetes, glucose intolerance Decreased sensation to pinprick and fine touch, hypohidrosis and partial alopecia Usually follows trauma 82 yo M with Resistant Hand Lesions 82 yo M presented to OSH for evaluation of left hand lesion s/p dog bite Started on vancomycin, piperacillin-tazobactam Developed painful, hemorrhagic bullae over wound
12 History: Biopsy at OSH: acute inflammatory cellular exudate and granulation tissue Debrided at OSH for presumptive necrotizing cellulitis Left hand wound expands PMH: Hidradenitis Suppurativa, COPD, HTN, DM2, sinus bradycardia s/p PPM, MM SHx: Married, 60 pack year smoker, dog ROS: 5 lb unintentional wt loss/ 1 week, +Diarrhea Similar wound appears on right hand DDx: Neutrophilic Dermatosis: Pyoderma Gangrenosum, Sweet s syndrome Infectious: Bacterial, mycobacterial, protozoal, fungal, viral Vasculitis: ANCA-associated or medium vessel vasculitis Malignancy: Lymphomatoid granulomatosis
13 Exam and Tests: PE: Afebrile, VSS Pyoderma Gangrenosum Classic: inflammatory pustule rapidly enlarging ulcer w/ undermined, gun metal gray borders and cribiform scarring; legs Labs: WBC % Polys, 1% Bands CBC, CMP otherwise WNL Tissue cultures, ANCAs negative Path: Re-reviewed pyoderma gangrenosum Peristomal PG Atypical Pyoderma Gangrenosum More superficial ulcers or deep erosions with blue-gray, bullous border Usually on the hands, arms or face aka neutrophilic dermatosis of the hands Can be very delayed Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007):
14 Associated Diseases 50-70% have an antecedent, coincident or subsequent associated disease 20-30% inflammatory bowel disease 20% arthritis Seronegative arthritis, spondylitis of IBD, RA 15-25% hematologic disease AML, CML, hairy cell leukemia, myelodysplasia, monoclonal gammopathy More likely in atypical cases Chronic Atypical PG Most common associations: Myelogenous leukemia Myelodysplastic disorders Refractory anemias IgA paraproteinemia Course: acute, relapsing, chronic Relapsing or chronic more likely associated with underlying disease Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007): Hospital Course Labs: WBC 9.7/ Hb 9.1 / PLT 78 Systemic w/u for underlying disease initiated Disease continues to rapidly progress despite IV steroids
15 Pathergy Non-specific inflammatory response to intradermal trauma Papules, plaques, pustules, ulceration Used as a diagnostic test for Behcet s Disease 18g needle inserted at an angle through the dermis of the skin Lesions within 48 hours Elicited in a minority of cases DDx Pathergy Behcet s Disease Acute Febrile Neutrophilic Dermatosis Pyoderma gangrenosum Bowel-associated dermatosis-arthritis syndrome Rheumatoid arthritis
16 Systemic Workup for PG CBC, CMP, hepatitis panel, U/A ANA, ANCA, RF, ACL Ab/LAC SPEP, UPEP CXR Systemic Workup GI workup refused by primary team SPEP reveals abnormal banding pattern Hematology Consultation GI workup Treatment of PG AGENT DOSE PROS CLINICAL CONS Prednisone 0.5-1mg/kg/day Rapid onset Short term 2/2 SE Cyclosporine 4-5 mg/kg/day Rapid onset Azathioprine mg/day Easy long term use Dapsone mg/day Long term safety Slow onset Methotrexate mg/week Well-tolerated Mycophenolate 2-3 g/day Long term safety Slow onset Mofetil Thalidomide mg/day Colchicine mg/kg/day Minocycline, doxycycline 100 mg BID-TID Well-tolerated Often ineffective Infliximab 5mg/kg/wk IV at 0, 2,6 wks q 6-8 wk Rapid onset Well-tolerated Not FDA approved Diagnostic Procedure Bone marrow bx Complicated myelodysplastic syndrome 5qdel but pancytopenia, advanced age poor prognosis Adapted from: Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007):
17 Autoimmune Manifestations of MDS Isolated autoimmune phenomenon Pyoderma gangrenosum One week s/p first infusion of Infliximab 5mg/kg IV Acute systemic vasculitis Classic connective tissue disorder Rheumatoid arthritis Immune mediated hematologic abnormalities Hemolytic anemia, immune thrombocytopenia Asymptomatic serological immunologic abnormalities Positive RF, ANA Pinheiro et al. The 5q syndrome and autoimmune phenomena: report of three cases. Leukemia Research 30 (2006) yo F from the Middle East with chronic idiopathic perianal wounds x3 years complicated by fistulas Initially presented with abscess, doctors there concerned for Crohns disease Started on infliximab, later developed anaphylaxis Switched to adalimumab and azathioprine, disease progresses Evaluated in London 2013: colonoscopy not c/w Crohns
18 Cutaneous Signs of IBD Prevalence of cutaneous manifestations of Crohns disease and Ulcerative Colitis ~ 9% 19/23% Three types of skin conditions: Specific: skin lesions have identical pathologic mechanisms to lesions of the GI tract (usually CD) Reactive: different pathologic features, likely cross antigenicity between skin and gut mucosa (CD,UC) Associated: likely relate to human leukocyte antigen linkage and chronic inflammation
19 Specific Lesions of Crohns Disease Fissures, fistulas Often contiguous with external mucous membranes Up to 36% of cases Presence of colitis is a positive predictor of perianal disease compared disease confined to the small bowel Granulomatous edematous inflammation on histology Specific Lesions of CD Oral disease: 8% to 9% of CD Swelling of the labia, gingiva, or mucosa; painful Mucosal and gingival cobblestoning Mucosal ulcerations and nodules Specific Lesions of Crohns Disease Metastatic CD Extension of inflammation to uncommonly affected sites Skin and subcutaneous; plaques, nodules, and ulcerations Predominantly extremities or intertriginous areas Histologically identical to CD Severity of CD does not necessarily correlate to skin disease Colon involvement seen more commonly in the setting of Metastatic CD Treatment of choice: treatment of underlying CD Does not guarantee therapeutic improvement of skin
20 Reactive Lesions of IBD Erythema nodosum (#1) Pyoderma gangrenosum, Sweet s syndrome Pyostomatitis vegetans Pyostomatitis Vegetans Superficial pustules and ulcerations, predominantly lips and buccal mucosa All reported cases associated with IBD Antiseptic mouthwashes and topical corticosteroids for temporary relief, treat IBD
21 Associated Conditions Psoriasis Alopecia areata Vitiligo Reactive arthritis Eczema Nail clubbing Acrodermatitis enteropathica Hidradenitis suppurativa Nodulocystic Acne 34 yo woman presents for cellulitis unresponsive to antibiotics s/p attempted I&D for possible abscess CBC reveals WBC = 80, smear c/f acute AML Diagnosis of AML confirmed after bone marrow biopsy Initiated on hydroxyurea with cytarabine/ idarubicin 7+3 induction Biopsy performed for histology and culture
22 Left lateral lower leg Carcinoma Erysipeloides Well-circumscribed, erythematous, warm, firm plaques Underlying malignancy Breast*, gastric, uterine, cervical, colon, GU, prostate, nasopharyngeal, mesothelioma, idiopathic Leukemia cutis
23 Breast Carcinoma Erysipeloides A.Marneros Carcinoma en cuirasse Fibrosis Induration Peau d orange H/o nearby cancer (breast) Bolognia Dermatology Fig 122.3
24 Breast Carcinoma Telangiectoides Conclusions Identify and differentiate cutaneous manifestations of systemic disease Learn systematic work-up for specific cutaneous findings Review treatment options Marneros A et al. JAAD 2009
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