Phildrich Teh MD MS Scripps Clinic CASE 68 yo Asian female with 4 months of recurrent urticaria Eval for underlying autoimmune disease autoinflammatory syndrome HISTORY PMHx ID: 1015007
Download Presentation The PPT/PDF document "WHEAL OF MISFORTUNE RWCS 2021" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
1. WHEAL OF MISFORTUNERWCS 2021Phildrich Teh, MD, MSScripps Clinic
2. CASE 68 yo Asian female with… 4 months of recurrent urticaria Eval for underlying autoimmune disease/ autoinflammatory syndrome
3. HISTORYPMHxOSADM IIHLDGERDPSHxI&D perirectal abscessFHxSister w/ SLESocHxHomemakerDenies ETOHNever smokerMedsMetforminRosuvastatinAllergiesPenicillin
4. INITIAL PCP VISITFor the past 3 months, 3 flares of illness lasting ~2 weeks eachUrticarial rashRaised, erythematous, pruritic but also painfulTrunk and limbsIndividual lesions resolve after 4 days then leaves hyperpigmented lesions and migratesNo angioedema, food triggers, no new meds other than metforminAssociated symptomsFevers (daily, 99.8-100.60F)Bone pain ( back, hips, shins) Arthralgias (hips and knees)
5.
6. PCP RECSWorkupCBC WBC 21k with neutrophilia / Platelets 490kTx: Medrol Pak Partial improvement
7. HEME and DERM VISITSHematology/OncologyDDx: Viral xanthem vs autoimmune vs hematologic such as lymphoma or leukemiaWorkup:(+) ANA 1:160 Homogenous, ESR 92, CRP 106(-) dsDNA, ANCA, SSA/B, flow cytometry panel, BCR/ABL (FISH)DermatologyPunch bx:Sparse perivascular and interstitial inflammatory infiltrate consisting of neutrophils and smaller numbers of lymphocytes compatible with urticaria with no evidence of fibrinoid necrosis/vasculitis. No IF staining done.Tx: IM triamcinolone 40mg x1, fluocinonide cream BID, loratadine 10mg BID, cetirizine 10mg daily
8. Classification of URTICARIAAcute urticaria: <6 weeksChronic urticaria: ≥6 weeksZuberbier T, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018
9. Zuberbier T, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018PainfulHyperpigmenation
10. ALLERGY VISITBx consistent with urticaria with no vasculitis but..Red flags:Individual wheals: 4 days to disappear, leaves hyperpigmented spots, and painfulFevers, bone pain, arthralgiasAssessment: Chronic urticaria/ concern for urticarial vasculitis vs underlying autoimmune diseaseWorkup(-) C3, C4, C1q, CH50Consider repeat skin biopsy with IFSee Rheumatology
11. RHEUM VISITComprehensive rheumatologic ROS negative other than:Urticarial rashFeverArthralgiaBone pain
12. WBC21kPlatelet490kHGB/HCTNormalCMPNormalESR92CRP106ANA1:160 HomogeneousdsDNANegativeANCANegativeSSA/ SSBNegativeRFNegativeC3/C4/C1q/CH50NegativeSkin BxSparse perivascular and interstitial inflammatory infiltrate consisting of neutrophils and smaller numbers of lymphocytesNo evidence of vessel wall necrosis to suggest vasculitisConsistent with urticariaBasic SerologiesIMMUNE SerologiesPATH REPORTBCR/ABL (FISH)NegativeFlow CytometryNegativeHEME Serologies
13. Systemic diseases W/ URTICARIACategoriesDiseasesVasculitis & CTDUrticarial vasculitis, GPA, EGPA, Cryoglobulinemia, SLE, Sjogren syndrome, DermatomyositisAutoinflammatory syndromesCryopyrin-associated periodic syndromes (CAPS), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Schnitzler syndromeHematologicMGUS, Waldenstrom macroglobulinemia, Non-Hodgkin lymphoma, Gleich syndromeInfectionsHepatitis B and CPeronia A, et al. Urticarial lesions: If not urticaria, what else? The differential diagnosis of urticaria. J Am Acad Dermatol. 2010
14. RHEUM VISITComprehensive rheumatologic ROS negative other than:Urticarial rashFeverArthralgiaBone painFamily hx of SLEDDxSchnitzler, TRAPS, CAPSHep B/CUrticarial vasculitisPlanSPEP, Periodic fever panel, Hep panel, Smith/RNPIf negative, repeat skin bx w/ IF
15. WBC21kPlatelet490kHGB/HCTNormalCMPNormalESR92CRP106ANA1:160 HomogeneousdsDNANegativeANCANegativeSSA/ SSBNegativeRFNegativeC3/C4/CH50NegativeC1qNegativeSmith/RNPNegativePeriodic Fever PanelNegativeSPEPIgM kappa monoclonalSkin BxSparse perivascular and interstitial inflammatory infiltrate consisting of neutrophils and smaller numbers of lymphocytesNo evidence of vessel wall necrosis to suggest vasculitisConsistent with urticariaBasic SerologiesIMMUNE SerologiesPATH REPORTBCR/ABL (FISH)NegativeFlow CytometryNegativeHEME SerologiesHep B/CNegativeINFECTIOUS Serologies
16. WHAT NEXT?Diagnosis:Schnitzler SyndromeTreatmentIL-1 inhibitor – anakinraFollow-upSymptom resolution within 2-3 days of treatmentReferral back to hem/onc for IgM gammopathy surveillance
17. SCHNITZLER SYNDROME
18. HISTORY and EpidemiologyFirst described by Liliane Schnitzler, a French dermatologist, in 19721Has since been reported in 25 countries worldwide (Europe, North America)Rare. As of 2017, total of 300 reported cases in the lierature2Male: Female ratio of 1.5 / Median age of 51 / Caucasian descent2Schnitzler L. Lésions urticariennes chroniques permanentes (érythème pétaloïde?). J Dermatol Angers. 1972De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
19. Clinical FeaturesChronic urticaria Intermittent Fever Arthralgia, rarely arthritisBone pain Pruritis Weight Loss Hepatomegaly Angioedema NeuropathySplenomegaly100%72%68%55%21%16%9%8%7%6% De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
20. CLINICAL FEATURESChronic urticariaRecurrent (few times a year to daily)Trunk and limbs mostlyIndividual lesions resolve in 24-48hrsBurning > pruritic sensationDe koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
21. Gusdorf L, et al. Schnitzler Syndrome: a Review. Curr Rheumatol Rep. 2017Gellrich FF, et al. Schnitzler syndrome. Hautarzt. 2019
22. CLINICAL FEATURESFevers≥ 38.0 0CArthralgias, rarely arthritisBack, hips, kneesBone painIliacs, tibia, fibulaDe koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014Gusdorf L, et al. Schnitzler Syndrome: a Review. Curr Rheumatol Rep. 2017
23. SEROLOGIESDe koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy 2014
24. IMAGINGScintigraphyIncreased uptake in 85%XrayHyperostosis in 39%De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
25. Skin BXNeutrophilic urticarial dermatosisPerivascular and interstitial infiltrate of neutrophils without significant edema or fibrinoid necrosis of the vessel wallsVasculitis seen in 20% (overestimation)IgM and IgG deposition in 30% of casesDe koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
26. STRASBOURG DIAGNOSTIC CRITERIASensitivity: 81% Specificity: 100%Sensitivity: 93% Specificity: 97%Simon A, et al. Schnitzler's syndrome: diagnosis, treatment, and follow-up. Allergy. 2013
27. TREATMENTIL-1 inhibitors are the treatment of choice1Efficacious (>90%)Rapid and sustained clinical responseIL-6 inhibitor in refractory casesStop treatment after 2 years and reassess (Strasbourg group)1Simon A, et al. Schnitzler's syndrome: diagnosis, treatment, and follow-up. Allergy. 2013De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
28. De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
29. COMPLICATIONSLymphoproliferative disease develops in 15 - 20% patientsWaldenstrom’s macroglobulinemia > Lymphomas > MMMonitored like other MGUS patients by hematologistsNo data whether IL-1 inhibition decreases risk AA amyloidosis in untreated patients, rare De koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014
30. PATHOPHYSIOLOGY UnknownNLRP3 mutationRationale: known mutations in Cryopyrin-Associated Periodic Syndrome (CAPS), a disease that is very similar to Schnitzler syndrome.Unlikely: NLRP3 mutation rarely seen in Schnitzler’s and would not explain MGUS or WaldenstromMYD88 mutationDe koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Transl Allergy. 2014Van leersum FS, et al. Schnitzler's syndrome - a novel hypothesis of a shared pathophysiologic mechanism with Waldenström's disease. Orphanet J Rare Dis. 2019
31. Van leersum FS, et al. Schnitzler's syndrome - a novel hypothesis of a shared pathophysiologic mechanism with Waldenström's disease. Orphanet J Rare Dis. 2019
32. SummarySigns of systemic involvement or atypical rash in chronic urticaria should prompt further evaluation:Vasculitis & CTDAutoinflammatory syndromesHematologic malignanciesInfection Schnitzler syndrome is a rare autoinflammatory syndrome characterized by chronic urticaria, a monoclonal gammopathy, and symptoms of systemic inflammation A condition that is often underdiagnosed IL-1 inhibition is an effective treatmentMonitor for lymphoproliferative malignancies
33. THANK YOU