58 yowoman referred for unresponsive drug rash
TRANSCRIPT
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
12:50 - 1:50pm
Can't Miss Dermatology Diagnoses: Cutaneous Manifestations of Systemic DiseaseSPEAKERDaniela Kroshinsky, MD MPH
Disclosures
►Daniela Kroshinsky, MD MPH: No financial relationships to disclose.
The following relationships exist related to this presentation:
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
• Learn other mimicking cutaneous conditions
58 yo woman referred for unresponsive drug rash
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Malignancy Screening • 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
Mimickers
31 yo W with anxiety, palpitations, and recurrent cellulitis
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
• 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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
•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
•Pertinent Labs: WBC 3.7, Hct 35, ESR 85, INR 3
• 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
•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
Course
•U/S demonstrates left popliteal vein thrombosis•Hematology increases INR goal to 3‐4, monitor
•Repeat aCL IgG 38 and B2GP1 9934•ANA 1:5120, dsDNA 1:80, Anti‐Sm and Anti‐RNPpositive
•Diagnosis: Systemic Lupus Erythematosus with secondary : Antiphospholipid Antibody Syndrome •Hydroxychloroquine 200 mg BID
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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 26.2 47.4%
‐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 (1998‐2004). 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. 2011 Mar 15:17(3):1.
32 year old W admitted for diarrhea and weight loss with itchy plaques on the legs
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
• Pruritic
• Present for 6 weeks
• Noticed after leg scratched on a bush
• Not improved with triamcinolone cream
DDx
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Necrolytic Acral Erythema
• First described in 1996
• Case series of 7 patients from Egypt with hepatitis C
• Patient’s Hepatitis Viral Load: 748,000
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%
• 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
Nejm.orgDermnz.net
• Up to 38% of patients with LP, especially associated with oral form
• Inquire esophageal ROS, genital involvement
HCV & Lichen Planus
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
• Biopsy at OSH: “acute inflammatory cellular exudate and granulation tissue”
• Debrided at OSH for presumptive necrotizing cellulitis
• Left hand wound expands
• Similar wound appears on right hand
History:
• 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
DDx:
• Neutrophilic Dermatosis: • Pyoderma Gangrenosum, Sweet’s syndrome
• Infectious: • Bacterial, mycobacterial, protozoal, fungal, viral
• Vasculitis: • ANCA-associated or medium vessel vasculitis
• Malignancy: • Lymphomatoid granulomatosis
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Exam and Tests:
• PE: Afebrile, VSS
• Labs:• WBC 9.1• 91% Polys, 1% Bands• CBC, CMP otherwise WNL
• Tissue cultures, ANCAs negative
• Path: Re-reviewed pyoderma gangrenosum
Pyoderma Gangrenosum• Classic: inflammatory pustule rapidly enlarging ulcer w/ undermined, “gun metal gray” borders and cribiform scarring; legs
Peristomal PG
• Can be very delayed
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
Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007): 787‐802.
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
• Course: acute, relapsing, chronic• Relapsing or chronic more likely associated with underlying
disease
Chronic Atypical PG• Most common associations:
• Myelogenous leukemia• Myelodysplastic disorders• Refractory anemias• IgA paraproteinemia
Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007): 787‐802
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Systemic Workup for PG• CBC, CMP, hepatitis panel, U/A
• ANA, ANCA, RF, ACL Ab/LAC
• SPEP, UPEP
• CXR
• GI workup
Systemic Workup
• GI workup refused by primary team
• SPEP reveals abnormal banding pattern
• Hematology Consultation
Treatment of PGAGENT DOSE PROS CLINICAL CONSPrednisone 0.5-1mg/kg/day Rapid onset Short term 2/2 SECyclosporine 4-5 mg/kg/day Rapid onsetAzathioprine 100-300mg/day Easy long term useDapsone 50-200 mg/day Long term safety Slow onsetMethotrexate 10-30 mg/week Well-toleratedMycophenolate Mofetil
2-3 g/day Long term safety Slow onset
Thalidomide 50-200 mg/dayColchicine 1.5-3 mg/kg/dayMinocycline, doxycycline
100 mg BID-TID Well-tolerated Often ineffective
Infliximab 5mg/kg/wk IV at 0, 2,6 wks q 6-8 wk
Rapid onsetWell-tolerated
Not FDA approved
Adapted from: Callen JP, Jackson MJ. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am. 33(2007): 787‐802
Diagnostic Procedure• Bone marrow bx
• Complicated myelodysplastic syndrome
• 5qdel but pancytopenia, advanced age poor prognosis
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Autoimmune Manifestations of MDS• Isolated autoimmune phenomenon
• Pyoderma gangrenosum
• 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) 507‐10.
One week s/p first infusion of Infliximab 5mg/kg IV
• 23yo 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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
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/ idarubicin7+3 induction
Biopsy performed for histology and culture
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Left lateral lower leg
Leukemia cutis
Carcinoma Erysipeloides
• Well-circumscribed, erythematous, warm, firm plaques
• Underlying malignancy
• Breast*, gastric, uterine, cervical, colon, GU, prostate, nasopharyngeal, mesothelioma, idiopathic
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Breast Carcinoma Erysipeloides
A.Marneros
Carcinoma en cuirasse
• Fibrosis
• Induration
• Peau d’orange
• H/o nearby cancer (breast)Bolognia Dermatology Fig 122.3
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Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Breast Carcinoma Telangiectoides
Marneros A et al. JAAD 2009
Conclusions• Identify and differentiate cutaneous manifestations
of systemic disease
• Learn systematic work-up for specific cutaneous findings
• Review treatment options