Dermatology Pearls for 2014American Board of Dermatology certifying exam

Michael W. Wangia, M.D.Clinical Assistant ProfessorDermatopathology Fellow

University of Florida Department of Dermatology

Objectives30 high-yield pearls

What I did to prepare

“For every pearl at the bottom of the ocean, there is a ton of whale shit.”

—Ernest Lee, M.D.

1. Ipilimumab Mechanism of action

Blocks CTLA-4 receptor†‡ on cytotoxic T lymphocytes, preventing their inhibition, allowing them to destroy melanoma cells

Adverse effects includeFacial swellingColitis

†Also known as CD152‡Normally CTLA-4 stimulation inhibits T-cells

2. Vemurafenib†

Mechanism of actionB-Raf protein inhibitor

IndicationTreatment of BRAF V600E mutation‡ positive unresectable or metastatic melanoma

†Also known as PLX4032 and by the brand name Zelboraf®‡Substitution of valine (V) with glutamic acid (E) at codon 600

3. DimethylaminopropylamineDMAPA is used in the formation of cocamidopropyl betaine

Cocamidopropyl betaine is found in liquid soaps and shampoos

DMAPA remains in products as contaminant

DMAPA is important cause of eyelid dermatitis

4. Angiopoietin receptorsTie-1 and Tie-2 are cell-surface receptors†

Angiopoietins bind these receptors and promote angiogenesis

There are four angiopoietins

Serum Ang2 levels are elevated in patients with angiosarcoma

†Mutations that lead to dysfunction of the Tie-2 receptor are associated with vascular malformations

5. Viral-associated trichodysplasiaClosely linked with organ transplantation, immunosuppression†, and pre-B cell leukemia

Follicular spiny papules erupt on face

Likely due to a polyomavirus‡

Treat with valganciclovir

†Cyclosporin often cited‡A dsDNA virus and member of papovavirus family

6. Merkel cell carcinomaMerkel cell polyomavirus (MCPyV)

Wide local excision

Sentinel lymph node biopsy in all cases

Adjuvant radiotherapy for lesions on head and neck with locoregional spread

7. Coding excision sizeMalignant lesions are excised with margins

Diameter of resulting surgical defect (lesion + margins) termed “excised diameter”

Excised diameter used to select proper CPT code to bill excision

A 6mm BCC on back excised with 4mm margins would result in a 1.4cm excised diameter (11602)

Modifiers

• -25• -59• -79

• Review these in the AAD website

8. Disseminated infundibulofolliculitis

Young dark-skinned patients

Uniform 1—2mm papules on neck and upper trunk

Figure 33-31 in Andrews’ 10th edition on page 776

Treat with topical steroids, PUVA or isotretinoin

9. SyringomasOccur not just on face but also neck, chest, axillae, upper arms, and periumbilically

Figure 111.22B in Bolongia’s 2nd edition on page 1704

Figure 29-36 in Andrews’ 10th edition on page 664

Associated with Down syndrome, Nicolau–Balus syndrome, and Brooke-Spiegler syndrome

10. Lupus miliaris disseminatus facieiRed-to-yellow papules on central face and around eyelids

Histology shows single superficial BB-like nodule

Central caseation necrosis

http://img.medscape.com/pi/emed/ckb/dermatology/1048885-1070740-268.jpg

11. Defects in keratin 5†‡

Epidermolysis bullosa simplex§

Dowling–Degos' disease

Olmsted syndrome

†For list of cutaneous conditions caused by mutations in keratins see: http://en.wikipedia.org/wiki/List_of_cutaneous_conditions_caused_by_mutations_in_keratins‡For more lists (some good, some not so good) of board-related fodder see: http://en.wikipedia.org/wiki/List_of_cutaneous_conditions#See_also §May be due to mutation in gene encoding keratin 5 and/or 14

12. “Migrating” conditionsCreeping eruption (Cutaneous larva migrans)

2cm/day

Larva migrans profundus (Gnathostomiasis)1cm/hour

Larva currens10cm/day

Erythema gyratum repens1cm/day

13. Schöpf–Schulz–Passarge syndrome

Ectodermal dysplasia

Diffuse symmetric palmoplantar keratoderma

Hypodontia

Multiple eyelid apocrine hidrocystomas

Syringofibroadenomas on extremities

Poromas

14. ErythrodontiaCongenital erythropoietic porphyria

Hepatoerythropoietic porphyria

15. Paraneoplastic pemphigusTarget antigens: desmoglein 1, desmoglein 3, BPAG1, plectin, desmoplakin 1, desmoplakin 2, envoplakin, periplakin, unknown antigen (170kDa)

Notably not BPAG2†

†Do not confuse the various BP antigen synonyms due to exam stress: BPAG1 (BP230)BPAG2 (BP180, type XVII collagen)

16. Eruptive xanthomasArise on buttocks and extensor surfaces of extremities

Hypertriglyceridemia

17. VoriconazoleAzole antifungal

Prophylaxis against Aspergillus infection

Accelerates development of SCC’s†

Photosensitivity‡ and premature photodamage†Skin cancer most frequent malignancy in organ transplant recipients (95% NMSC | SCC > BCC)‡UVA-induced like most medication-related photosensitivity

18. “Trench” conditionsTrench fever

Bartonella quintanaPediculus humanus corporis

Trench mouthMixed population of bacteriaPrevotella intermedia, Fusobacterium,

Treponema and Selenomonas spp.,

Trench foot

19. Defects in p genesp53

Li–Fraumeni syndromeActinic keratosesSquamous cell carcinoma

p57Beckwith–Wiedemann syndrome

p63Hay–Wells syndrome (AEC syndrome)EEC syndromeRapp–Hodgkin syndrome

20. Vismodegib†

Mechanism of actionAntagonizes membrane bound smoothened receptor leading to less activity of GLI transcription factor and ultimately decreased expression of tumor mediating genes‡

Adverse effects includeMuscle spasmsAlopecia

†Used to treat locally advanced or metastatic BCC’s‡Inactivating PTCH mutations and activating SMO mutations cause most BCC's. Normal pathway: SSH binds PTCH, together they inhibit SMO leading to less GLI transcription factor going to nucleus (net result: decreased expression of tumor mediating genes).

21. Becker’s nevusAssociated with a smooth muscle hamartoma

Transient induration/elevation upon rubbing in 80% (pseudo-Darier's sign)

May occur on the forehead, cheek, chest, shoulder, forearm, wrist, abdomen, buttock, and shin

22. Cold panniculitisCheeks of toddlers and young children

Results from contact with popsicle or ice bag

No treatment necessary

23. Extracellular matrix protein-1ECM-1 mutated in lipoid proteinosis†‡

Targeted by autoantibodies in lichen sclerosus

†Also know as Urbach–Wiethe disease‡Beaded papules on eyelid margin not the only finding. First clinical sign is weak cry due to deposition of hyaline-like material in laryngeal mucosa. Hoarseness remains throughout life. “Ice-pick”-like acneiform scars occur on face.

24. Collagen types in cartilageII (2)†

IX (9)†

X (10)XI (11)†

XII (12)XX (20)XXVII (27)

†Autoantibodies to collagen type 2, as well as 9 and 11, have been reported to cause relapsing polychondritis. This targeting of cartilage results in the red ears (sparing the lobes), arthritis, aortic aneurysms, and tracheal collapse.

25. ClofazimineMechanism of action

Unknown

IndicationMultibacillary leprosy (>5 lesions)

Adverse effects includeOrange–pink skin and body fluid discolorationIchthyosisFatal enteropathy†

†Due to crystal deposition in the small bowel mucosa

26. GNAS1 geneEncodes G protein α-subunit that regulates adenylate cyclase activity

Normal function is to negatively regulate bone formation

Mutated in several conditions includingProgressive osseous heteroplasiaPlate-like osteoma cutisAlbright hereditary osteodystrophyMcCune–Albright syndrome

27. WHIM syndromeWarts

Hypogammaglobulinemia

Infections†

Myelokathexis‡

Mutated chemokine receptor CXCR4 gene§

†Namely recurrent bacterial infections such as sinusitis, cellulitis, periodontitis, and meningitis‡Chronic peripheral neutropenia due to retention of neutrophils in the bone marrow§Autosomal dominant

28. Paraphenylenediamine (PPD)Common contact allergen found in

Black hair dye, scuba gear, henna†

Cross-reacts withPara-aminobenzoic acid (PABA), azo dyes, sulfonamides/sulfonylureas, thiazides, ester anesthetics‡

Neutrophilic and eosinophilic dermatitis†Not found in pure henna‡PPD + PASTE

29. OmalizumabMechanism of action

Humanized monoclonal IgG1 antibody that binds to IgE preventing interaction with receptor (FcϵRI) on mast cells and basophils

Has been used to treat urticaria, atopic dermatitis, and bullous pemphigoid†

†IgG not only circulating auto-antibody isotype in bullous pemphigoid, but also IgE

30. Oral fibromaMost common “tumor” of the oral cavity

Located along bite line of the buccal mucosa

Cured by conservative surgical excision

Miscellaneous RandomsImatinib/Gleevec

• Treatment of DFSP with + PDGFR-COL1A1 mutation

• Treatment of hypereosinophilic syndrome with mutation in FIP1L1-PDGFR alpha mutation.

IP

• Mutation? NEMO. Affects NF-KB. What is the purpose of NF-KB? - protects against TNF-induced apoptosis

Vascular lesions?

• Wiebel palade bodies. These are essentially storage granules of endothelial cells. Contain vWF and P-selectin. Play dual role in both hemostasis and inflammation

• Bier spots are small erythematous blanching macules. Essentially benign physiologic vascular anomaly of no significance clinically. Know both malignant and benign vascular tumors and lesions.

Fibromatosis

• Juvenile hyaline fibromatosis – (nodular lesions on hands, scalp and face with gingival hypertrophy and associated joint contractures). Bx shows nodular hyaline fibrosis). Genetic mutation associated? CMG2 (capillary morphogenesis protein-2). Or ANTXR2 mutations (anthrax toxin receptor 2).

What I did to prepareNote taking and memorization

Clinical images

Pathology

Practice questions

Note taking and memorization (I) Leading up to month prior to exam

Read through and took notes from Bolognia’s – put more emphasis on photos and tables entire 2nd edition (ISBN 1416029990)

Read entire Andrews 2 months prior to the boardsSpent 2 weeks prior to the test day My goal was to review, re-review, and memorizing above notes every two weeks

Note taking and memorization (II)During one month prior to exam

Skimmed Genodermatoses (i.e. "Spitz" | ISBN 0781740886) and added to my notes when needed

Reviewed notes from 2013 Florida Dermatology & Dermatopathology Board Review Course

Re-reviewed my own notes

Clinical imagesDuring one month prior to exam reviewed all images in:

Andrews’ 11th editionsBolognia’s 2nd editionColor Atlas of Dermatology 1st and 2nd editions (i.e. "Callen" | ISBN 0721637566 and 0721682561)

Atlas of Clinical dermatology 4th ed Du Vivier

DermatopathologyDuring one month prior to exam†

Reviewed Elston front to back Watched all the PowerPoint lectures by Dr. Elston

found on the Dermatopathology: Requisites in Dermatology website‡

Reviewed all the online DLCS study slide sets§

†Note: I also attended two review courses, the Barron Board Review and the Florida Dermatology & Dermatopathology Board Review Course, both of which had slide reviews‡http://www.requisitesindermatology.com/dermatopathology_ppt.php§http://dermpathlab.com/residents/slide-study-set-program

Practice questionsDuring one month prior

Reviewed all ETAS practice questions†

Reviewed all questions in the ASDS Primer in Dermatologic Surgery: A Study Companion‡

†http://dermatologyinreview.com/Galderma‡http://www.asds.net/primerbook.aspx

What I did NOT do to prepareGalderma Preboard Seminar review courseQuizes in McGraw-Hill Specialty Board Review

Dermatology: A Pictorial Review (ISBN 0071597271)

Journal review

• **** REVIEW SCLEROTHERAPY (slerosing agents, side effects etc); HAIR TRANSPLANTATION; AND FOCUS ON TECHNIQUE AND MAJOR COMPLICATIONS.

• - Recommend using Bolognia and Surgery Primer

Questions?

ReferencesBooks (ISBN):

Andrews' Diseases of the Skin: Clinical Dermatology (1437703143)Dermatology (0723435715)Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence (1437704123)

Papers (PMID):A review of radiotherapy for merkel cell carcinoma of the head and neck (23213534)Clofazimine: a review of its medical uses and mechanisms of action (7829710)Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway (22431713)Disseminate and recurrent infundibulofolliculitis: response to isotretinoin (15303788)Eyelid dermatitis: contact allergy to 3-(dimethylamino)propylamine (9134437)Human papillomavirus typing of verrucae in a patient with WHIM syndrome (20713842)Neutrophilic and eosinophilic dermatitis caused by contact allergic reaction to paraphenylenediamine in hair dye

(23165836)Observations on angiopoietin 2 in patients with angiosarcoma (15149523)Routine omission of sentinel lymph node biopsy for merkel cell carcinoma <= 1 cm is not justified (19933899)Schöpf-Schulz-Passarge syndrome: further delineation of the phenotype and genetic considerations (19002348)Skin cancer in solid organ transplant recipients: advances in therapy and management (21763561)Successful treatment of bullous pemphigoid with omalizumab (23165827)The genesis of Zelboraf: Targeting mutant B-Raf in melanoma (23027900)Trichodysplasia of immunosuppression treated with oral valganciclovir (19103376)Viral-associated trichodysplasia in patients who are immunocompromised (14726896)Voriconazole-associated phototoxicity (21382298)

• Thank Dr. Brendan Thomas for his input

wangim@dermatology.med.ufl.edu