Greatest Cases from OHSU Dr

6/30/2015

Greatest Cases from OHSU Dr. Matthew Majerus, Chief Resident

Case #1

• 34 y/o otherwise healthy male • 6-month history of sporadic blisters on hands and arms • Denies worsening with sun exposure, residual scarring, or hair growth • On questioning, also notes 8-month history of loose stools compared to his baseline • Lives with girlfriend, she has no symptoms

Initial Exam and Plan

• Exam = normal • Serum IgA = normal • Tissue transglutaminase = normal • Return to clinic for biopsy if blisters return

1 6/30/2015

3 Months Pass…..

• Awoke with two pruritic vesicles, presents for biopsy

H&E, 2.5x

H&E, 20x

2 6/30/2015

Biopsy Results

• H&E: Massive papillary edema with nodular/diffuse dermatitis with eosinophils and neutrophils. Consistent with bullous arthropod bite reaction.

• Direct Immunofluorescence: no diagnostic immunopathologic changes

20 Hours After Biopsies

Linear Red Streak in Setting of Recent Biopsy

• Pruritic, not painful • No fever/sweats/chills • No drainage or tenderness • No lymphadenopathy • Plan: antihistamines, bacterial culture, and cover for possible infection with antibiotics • Close follow-up

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Superficial Lymphangitis After Arthropod Bite

Superficial Lymphangitis After Arthropod Bite • Often mistaken for bacterial lymphangitis and treated with antibiotics • Rare reaction • Review article in 2008 with a case series of 6 patie nts + lite ratu re re vie w: – No fever or lymphadenopathy – Pruritic eruption, not painful – Spreads over 12-20 hours, disappears spontaneously in a few days – No lab abnormalities (CRP, ESR, WBC)

Case #2

• 57 yo Caucasian woman with h/o ESLD due to autoimmune hepatitis underwent orthotopic liver transplant 15 days after acute hepatic decompensation • Grafted liver responded well with decreasing LFTs and total bilirubin • She was placed on an immunosuppressive regimen and antimicrobial prophylaxis per transplant protocol

4 6/30/2015

Case #2

• Course complicated by Aspergillus pneumonia treated with Voriconazole and tracheostomy for recurrent respiratory failure • 3 weeks post-op, had acute rise in LFTs • Liver biopsy – non-specific reactive changes • ERCP – biliary stricture, stent placed • Developed diffuse rash on trunk and extremities so Dermatology was consulted on POD 35

Clinical Photos

Differential Dx

• Drug hypersensitivity reaction – Elevated eosinophils, LFTs at time of onset • ?Voriconazole (already d/c) • Scabies – Finger papules, volar wrist linear excoriations • Scabies prep negative • Infection – Immunosuppressed, h/o aspergillus • Tissue culture negative

5 6/30/2015

Histology

3 days later…

Differential Dx

• Graft Versus Host Disease – Biopsy showed vacuolar dermatitis – Stool studies negative for infectious diarrhea • Stevens Johnson Syndrome – Bactrim d/c, posaconazole unlikely • Herpes Simplex Virus – On prophylaxis, PCR negative

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GVHD in liver transplant

• Mortality rate is very high (85-100%) • Increased risk of GVHD in transplant pts with h/o autoimmune hepatitis • Donor cells attack host so there is no liver involvement, no abnormal LFTs • Frequently develop pancytopenia

Diagnosis

• Transplant op note confirmed she received liver from a male donor • FISH analyyysis on skin biopsy can tell if the lymphocytes in the skin are donor XY cells • Found to have 8% XY cells confirming diagnosis of GVHD • Underwent colonic mucosal biopsy consistent with GVHD

Diagnosis

7 6/30/2015

Management

• Decrease immunosuppression to allow host to destroy donor cells – Started on 4-week course of Etanercept – Continued on Solumedrol and Tacrolimus • Monitor CBC for pancytopenia – Developed severe pancytopenia and started on Neupogen – Bone marrow biopsy for HLA typing in anticipation of bone marrow transplant

Follow-Up

• Over the next 24 hours, developed septic shock due to pneumonia, bacteremia, anuric renal failure, myocardial ischemia • Made comfort care on POD 76 and passed away shortly thereafter

References

• Post GR, Black JS, Cortes GY, Pollack RB, Wolff DJ, Lazarchick J. The utility of fluorescence in situ hybridization (FISH) analysis in diagnosing graft versus host disease following orthotopic liver transplant. Ann Clin Lab Sci. 2001 Spring; 41(2) 188-92.

• Rogulj IM, Deeg J, Lee SJ. Acute graft versus host disease after orthotopic liver transplantation. J Hematol Oncol. 2012 Aug 13; 5:50.

• Zhang C, Yang G, Ling Y, Chen G, Zhou T. Graft versus host disease following liver transplantation: A case report. Exp Ther Med. 2014 Oct; 8(4) 1164-1166.

8 6/30/2015

Case #3

• 49 yo F with >1 yr swelling, pain, pruritus B LEs – Developed red painful bumps • Started with trauma to R leg – Resolved with prednisone, then relapsed • On pred x 6 months – Intolerant to MTX – Started on colchicine, unclear efficacy after 1 mo tx

Case Presentation

• PMH: Rosacea • FH: father – RA • Meds: colchicine, tylenol, ibuprofen, minocycline • ROS: weight gain, fevers, loss of appetite

Physical Exam

9 6/30/2015

Physical Exam

Labs

• ESR: 48 • Eosinophilia • Fungal testing (aspergillus, blastomyces, cocci, histo) negative • Hep B/C (-) • UA normal • ANA (+), pANCA (+), dsDNA (+) • C3, C4 normal •CXR wnl

Pathology

10 6/30/2015

Pathology

Key historical findings

• On minocycline > 1 year for rosacea • MCN stopped while on moxifloxacin (sx improved) • WkiDWorking Dx: MINOCYCLINE-INDUCED CUTANEOUS POLYARTERITIS NODOSA

Polyarteritis Nodosa

• Segmental necrotizing vasculitis of medium arteries – Deposits of C3, IgM, fibrin in walls of vessels • Pathogenesis – Infectious: HBV, HCV, strep, parvovirus B19, HIV – Neoplastic: hairy cell leukemia – Inflammatory: IBD, SLE, FMF – Drug: minocycline • Classic vs cutaneous (10%) variants

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ACR Diagnostic Criteria for systemic PAN

• Livedo racemosa • Polymorphonuclear arteritis • Leg pain/myopathy/weakness (-) ANCA • Mono-/polyneuropathy • Positive HBV serology • Weight loss > 4kg • Testicular pain/tenderness • Diastolic blood pressure > 90 mmHg • Elevated BUN/creatinine • Arteriographic abnormality (microaneurysms)

Cutaneous variant

• Cutaneous polyarteritis nodosa – Necrotizing vasculitis of the medium vessels – ANCA negative • Cutaneous PAN: 10-20% + pANCA – Differentiated from PAN by lack of systemic symptoms

– Very rare (<3% of all vasculitis)

Chen and Carlson. Clinical Approach to Cutaneous Vasculitis. Am J Clin Dermatol 2008. 9 (2):71-92 Ishigura and Kawashima. Cutaneous polyarteritis nodosa: A report of 16 cases with clinical and histopathological analysis and a review of the published work. JOD. 2010. 37: 85–93.

Cutaneous variant

•F > M – 20s to 40s • Lower extremities – Tender nodules – Livedo reticularis/racemosa –Ulcers – Acral gangrene – Neuropathy 22-66% • Associated fatigue and myalgia

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MCN-induced PAN

• 27 reported cases • Common presenting symptoms: – Fatigue, myalgias, arthralgias, weight loss, testicular pain, peripheral neuropathy • One case of 26 yo presenting with ischemic pontine stroke – She had livedoid, erythematous patches x 6 months prior

Proposed criteria for dx

• 6 of the following 7 – MCN use > 12 months – Skin manifestations: livedo reticularis, subcu nodules – arthritis or myalgias or neuropathy in distribution of rash – Lack of systemic organ involvement* – Skin biopsy with necrotizing vasculitis of small to medium-sized vessels – + pANCA – Improvement after discontinuation of MCN

Culver B, Itkin A, Pischel K. Case report and review of minocycline-induced cutaneous polyarteritis nodosa. Arthritis Rheum. 2005 Jun 15;53(3):468-70.

Case follow up

• Prednisone taper • Stopped minocycline

• On follow-up, her skin findings had resolved

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References

1. Bolognia, J. L., Jorizzo, J. L., Schaffer, J. V. (2012). Dermatology, 3rd Ed. Saunders 2. Klaas JP, Matzke T, Makol A, Fulgham JR. Minocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem stroke. J Clin Neurosci. 2015 Mar 13. pii: S0967-5868(14)00719-x. 3. Culver B,,, Itkin A, Pischel K. Case rep ort and review of minocycline-induced cutaneous polyarteritis nodosa. Arthritis Rheum. 2005 Jun 15;53(3):468-70. 4. Lightfoot Jr RW, Michel BA, Bloch DA, Hunder GG, Zvaifler NJ, McShane DJ, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33(8):1088-93. 5. Hernandez-Rodriguez H, Alba MA, Prieto-Gonzalez S, Cid MC. Diagnosis and classification of polyarteritis nodosa. J Autoimmun. 2014 Feb-Mar;48-49:84-9

Case #4

• 4 yo M born at term from uncomplicated pregnancy to nonconsanguineous parents with unremarkable family history

• Presents with developmental delay (language, social, cognitive), multiple skin lesions

• At birth he was noted to have right sided ‘red flat rash’ that loo ke d like ‘he was s tung by a je lly fis h’

• Over time evolved to hypopigmented streaks now becoming thickened with numerous papules

• Coarse hair growth on right arm and leg

• Right thumb is broad, misshapen

Physical Exam

• Hypopigmented, slightly atrophic smooth papules and plaques studded with ice pick-like scarring and open comedones in Blaschk o-linear distribution involving majority of R side of body

• Hyperpigmented atrophic papules and plaques on R foot

14 6/30/2015

Physical Exam

• Hypertrichosis on R anteromedial thigh and R upper arm (not shown)

• Broad (double in width) irregularly shaped R thumb with deep fissure

• Outside imaging: – R hand X-ray: duplicated metacarpal, duplicated proximal and distal phalanx –Brain MRI: Cystic abnormality involving R ventricle

Histology

5X • Strands of basaloid cells in fibrotic stroma surrounding partially dilated follicular infundibulum consistent with 10X basaloid follicular hamartoma

Happle-Tinschert Syndrome (aka Basaloid follicular hamartoma syndrome)

• Approximately 12 cases reported – Often under different designation but with same clinical features

• Unilateral, Blaschko-linear basaloid follicular hamartomas – Cutaneous lesions can be associated with milia or comedonal-like umbilication – Lesions can become more papular and hyperpigmented over time, specifically around puberty

• Ipsilateral extracutaneous defects include: – Skeletal: polydactlyly, over or deficient growth of ipsilateral limbs, cervical ribs – Dental: anodontia, hypodontia – CNS: Developmental delay, meningioma, optic glioma, arachnoid cysts, ventricular cysts

• Mosaic, genetic defect not yet identified, 3:1 M:F – Previously hypothesized to be related to Gorlin syndrome (aka nevoid basal cell carcinoma syndrome) but all cases tested for PTCH gene mutation have been negative

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References

1. Happle, R and Tinschert, S. Segmentally arranged follicular hamartomas with osseus, dental, and cerebral anomolies: A distinct syndrome. Acta Derm Venereol 2008; 88: 382-386. 2. Iten, PH. Happle-Tinschert syndrome. Dermatology 2009; 218: 221-225. 3. Boccaletti, V et al. Congenital systematized basaloid follicular hamartoma with microphthalmia and hemimegalencephaly. Pediatric Dermatology 2011; 28(5):555-560.

Case #5

• 8 day old female • Born at 29 weeks gestation – Caucas ian mo ther an d fa ther • Pregnancy complicated by fetal anemia necessitating two intrauterine transfusions – 26 & 27wks

Case #5

• Total bilirubin elevated at 12 hrs after birth – intensive phototherapy was initiated • Ruddy after birth • Increasing brown grey skin discoloration over following 48hrs • Consult placed for changing skin color

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• Family History – 4 yo sister born at 32 weeks – h/o fetal hydrops, hydrocephalus, hearing loss, cardiac malformation,,p transfusion dependent anemia – s/p BMT no longer needing transfusions – had similar discoloration after birth – also underwent phototherapy as neonate – discoloration resolved several weeks after birth

17 6/30/2015

Patient’s sister at birth and at a few weeks of life

Differential

• Bronze baby syndrome • Chediak-Higashi syndrome • Unusual jaundice • CbCarbon bbbaby syn drome – universal acquired hypermelanosis • Chloramphenicol intoxication – gray baby syndrome

Diagnosis

• Bronze Baby Syndrome (BBS): – Characterized by development of a dark gray- brown discoloration of the skin, serum, and urine with phototherapy – Seems to depend on presence of hyperbilirubinema, cholestasis, and phototherapy – First described by Kopelman et al. in 1972

18 6/30/2015

Discussion

• Pathogenesis unclear • Accumulation of bilirubin photoproduct • Cholestasis results in decreased elimination of pigment • But, not all babies with cholestasis develop BBS during phototherapy

A. McDonagh J Pediatr 2011

• Neonatal Jaundice: – Appox 60% of normal newborns become clinically jaundiced – Some require phototherapy as bilirubin is potentially toxic to the CNS – Blue light leads to more water soluble bilirubin photoisomers that can be eliminated

Management

• No intervention for pigment necessary – Pigmentation slowly returns to normal with discontinuation of phototherapy (5-20 days) – Phototherapy normally continued as needed for hyperbilirubinemia • Babies that develop BBS should be investigated for possible underlying liver disease • Caution in monitoring O2 saturation as pigment has been reported to interfere with pulse oximetry reading • If pigment does not resolve with discontinuation of phototherapy investigate alternative diagnosis

SA Hussain J Perinatology 2009

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Clinical Course

• Total Bilirubin decreased with phototherapy so phototherapy was stopped • Color faded rapidly after discontinuation of phototherapy

4 days after stopping phototherapy

2 weeks after stopping phototherapy

SPTA1 Mutation

20 6/30/2015

• Bronze Baby Syndrome (BBS): – Rare condition characterized by development of a dark gray-brown discoloration of the skin, serum, and urine with phototherapy – Requires hyperbilirubinema, cholestasis, and phototherapy – Exact pigment unknown, thought to be photo product of bilirubin – Pigmentation resolves with cessation of phototherapy

References

• Kopelman AE, Brown RS, Odell GB. The ‘‘bronze’’ baby syndrome: a complication of phototherapy. J Pediatr 1972;81:466-72. • Rubaltelli FF, Da Riol R, D’Amore ESG, Jori G. The bronze baby syndrome: evidence of increased tissue concentration of copper porphyrins.Acta Paediatr 1996;85:381-4. • Jori G, Reddi E, Rubaltelli FF. Bronze baby syndrome: evidence for increased • serum porphyrin concentration. Lancet 1982;1:1072. • Jori G, Reddi E, Rubaltelli FF. Bronze baby syndrome: an animal model. • Pediatr Res 1990;27:22-5. • Rubaltelli FF, Jori G, Reddi E. Bronze baby syndrome: a new porphyrin related • disorder. Pediatr Res 1983;17:327-30. • Hussain SA. Pulse oximetry interference in bronze baby syndrome. • J Perinatol 2009;29:828-9 • McDonagh AF, Phototherapy for Neonatal Jaundice. New England Journal of Medicine 2008 • McDonagh AF, Bilirubin, Copper-Porphyrins, and the Bronze-Baby Syndrome J Pediatr 2011;158:160-4

Thank you!