What Can We Glean from the Largest Organ in the Body?

1. Clinical Pearls in DermatologyLisa H Scatena, M.D. F.A.A.D.Rocky Mountain Dermatology, BoulderAssistant Clinical ProfessorDermatology & Internal Medicine University of Colorado, Denver6 February 2009

2. What Can We Glean from the Largest Organ in the Body?

3. What Can We Glean from the Largest Organ in the Body? Earlier detection, diagnosis and treatment of systemic diseases.

4. Where Have We Been and Where Are We Going? • 2006- The skin biopsy • 2008- Common dermatoses • 2009- Systemic diseases and skin findings • 2010- ?

5. Learning Objectives • Recognize newly described skin diseases • Review newer skin signs of well-established systemic diseases • Based upon skin findings, make appropriate diagnostic and therapeutic decisions for systemic diseases

6. Case 1

7. Case 1: A 54 year old man with diabetes mellitus and chronic renal failure complains of swelling, tightness and darkening of the skin on his arms and legs. His symptoms have developed over the past 2-3 weeks following a failed kidney transplant and imaging. Upon further questioning, this patient is most likely to also complain of:

8. 0 Case 1: Upon further questioning, this patient is most likely to also complain of: • Burning and itching in his arms and legs • Changes in his vision • Colicky abdominal pain • Difficulty swallowing • Oral ulcers

9. Nephrogenic Fibrosing Dermopathy • 15 patients with renal disease • Extensive thickening and hardening of the skin with brawny hyperpigmentation • Nearly all had extremity lesions, tendency to spare the trunk • Some had diffuse thickening, others papules or subcutaneous nodules Cowper et al. Lancet 2000; 356:1000

12. CD 34

14. Nephrogenic Fibrosing Dermopathy • Fibrosis may lead to calcification and dermal ossification • Extension from skin and subcutaneous tissue into the underlying fascia and muscle • Flexion contractures continue to worsen with resultant severe disablility • Increased mortality

15. Nephrogenic Fibrosing Dermopathy

16. Nephrogenic Fibrosing Dermopathy • The dominant cell is a dual staining CD34-procollagen fibrocyte corresponding to a circulating cell that expresses markers of both connective tissue cells and leukocytes • Aberrant fibrocyte recruitment, activation or proliferation the cause? Possibly related to ischemia Curr Opin Rheumatol 2003, 15: 785

17. CD 34

18. Nephrogenic Fibrosing Dermopathy • 33 patients in St Louis with NFD • Most had received dialysis • Only 1 patient had not been exposed to gadolinium • 4/33 had NOT been exposed to gadolinium for more than a year (range: 16-68 months) • Gadolinium exposure has some causative role in NFD. CDC NFD associated with exposure to gadolinium-containing contrast agents-St Louis, Missouri, 2002-2006. MMWR 2007 Feb 23;56;137-41

19. Nephrogenic Fibrosing Dermopathy • Cross sectional study of 186 dialysis patients in Boston • 25/186 had NFD skin changes identified (13%) • 94% had exposure to Gadolinium • Mortality rate among dialysis patients with NFD was statistically greater than “usual” dialysis patients • NFD is a predictor of early mortality. Todd et all. Cutaneous changes of NSF. Predictor of early mortality and associated with gadolinium exposure. Arth Rheum 2007 Sept 28;56:3433.

21. Nephrogenic Fibrosing Dermopathy • Topical steroids, retinoids, and lactic acid, systemic retinoids, and electron beam all tried without effect • Individual patients have responded to prednisone,plasmapheresis, IVIG, thalidomide, UV-A1, extracoporeal photopheresis and interferon-alpha, many others have not • Improvement of renal function or transplantation may improve NFD, but not always • Current favored therapy is PREVENTION BJD 2005; 152: 531

22. PEARL #1Consider alternate imaging processes when possible in patients with renal failure. If a patient must have an MRI, prompt dialysis after MRI is suggested.

24. This 63 year old man has been on this medication for years. Not only has he experienced the skin changes below, he has developed arthralgias and a (+) ANCA.

25. 10 Causative agents for his skin changes include: • Amiodarone • Gold • Minocycline • Plaquenil

26. Well known agent to result in hyperpigmentation as a result of both melanin and iron deposition Locations Blue-black scars Blue gray legs & forearms Muddy brown on sun exposed areas Reported to cause a lupus-like syndrome (+) ANA, (+) pANCA Occurs at a greater rate in those patients on minocycline for longer duration of time Resolves when minocyline is discontinued Minocycline

27. PEARL #2If a positive ROS is elicited for connective tissue disease in minocycline recipients, consider serologic testing including ANCA.

28. Case 3: Looking at What We Know from A Different Vantage Point…

29. Courtesy of Dr. William James

30. 10 Case 3: A 56 year old woman with arthralgias, malaise, scaling scalp, and intractable itching develops this bizarre eruption. What other findings would you expect on examination? • Deep red-violaceous patches on extensor forearms • Lichenified, excoriated plaques periumbilical area • Scarring alopecia • Violaceous tender nodules on shins

31. DermatomyositisCentripetal Flagellete Erythema • Edematous, erythematous streaks on the trunk and proximal extremities • Histology – interface dermatitis, positive direct immunofluorescence • Parallels disease activity • Only reported in dermatomyositis, not seen in other connective tissue diseases, in a review of 183 patients from one institution Arch Dermatol 2000; 136: 665 J Rheumatol 1999; 26: 692 Arch Dermatol 2000; 136: 665 J Rheum 1999;26:692

34. Dermatomyositis

36. Dermatomyositis:Gingival Telangiectases • Five patients with juvenile DM • 1 boy, 4 girls • All had similar nail fold telangiectases • Other oral findings of DM include edema, erosions, ulcers and white plaques Arch Dermatol 1999; 135: 1370

37. 10 What finding is most predictive of an underlying malignancy in DM? • Cutaneous Necrosis • Gottron Papules • Itching • Mechanics Hands • Shawl sign

39. DermatomyositisCutaneous Necrosis • Cutaneous necrosis – rare in adults • 1990: 5 cases reported in a study of 32 patients with dermatomyositis • In 4 of 5 cases, patients had associated malignancy • 7 of 10 in a larger series had malignancy • Positive predictive value of cutaneous necrosis is 71.4% • Cause uncertain, some with antiphospolipid antibodies Arch Dermatol 2003; 139: 539

40. DermatomyositisRisk of Internal Malignancy • Classic dermatomyositis has a definite association with occult malignancy <25% • Women: ovarian carcinoma • Asian men: nasopharyngeal carcinoma • Negative risk factor: Interstitial lung disease • Little-to-no increase risk of malignancy in polymyositis Lancet 2001; 357:85-86 Br J Cancer 2001; 85:41-45 Curr Opin Rheumatol 2000; 12:498-500

41. DermatomyositisWhat about cutaneous amyopathic DM? • Sontheimer reviewed world literature which reported a total of 300 cases • 10% of these were associated with malignancy • Mayo Clinic 1976-1994 found 32/746 patients had cutaneous amyopathic dermatomyositis • 25% found to have malignancy in 2-10 year follow-up • All were women • Lung CA, ovarian CA, breast CA, endometrial CA and metastatic adenocarcinoma of unknown primary Dermatol Clin 2002; 20:387-408

42. DermatomyositisOccult Malignancy Work-up • Repeat malignancy surveillance measures every 6-12 months for the first 3-5 years following the diagnosis • After 5 years, the risk of malignancy returns to that of the general population for that age and sex Dermatol Clin 2002; 20:387-408

43. PEARL #3In the case of a new diagnosis of dermatomyositis in an adult, at a bare minimum, age appropriate screening for malignancy should be performed. Strongly consider imaging if clinically indicated.

44. Case 6 month history of this minimally itchy eruption. Started with 1 red patch and spread after application of a prescription medication.

45. 10 What prescription medication did he put on his skin with this resultant rash? • Efudex • Eucerin Calming Lotion • Neosporin ointment • Retin-A cream • Triamcinolone cream

47. Tinea Versicolor • Not really a dermatophyte, caused by Malassezia furfur or pityrosporum ovale • As a yeast, considered normal follicular flora • As hyphae, results in skin disease • Common in summer months • Treatment • Azoles,selenium sulfide lotions, Zinc pyrithione soap • PO Azoles for difficult to treat cases • Ketoconazole 400mg doses repeated monthly • Itraconazole 200mg qd x7days • Fluconazole 400mg once monthly

48. PEARL #4If there is scale, SCRAPE IT!!

49. 64 year old man presents with asymptomatic 1-2mm firm, white-flesh colored bumps all over his face since his 30’s. 5. • PMHx: HTN, history of pneumothorax • Medications: Lisinopril, ASA • Wears sunscreen routinely • 5-10 blistering sunburns in his lifetime

50. Our patient: