Peter Saitta, DO Associate Clinical Professor The Classification and Treatment of

2 . Period prevalence . Risk factors . Classification systems . Differential diagnosis . First-line therapy options

Objectives 3 . Prevalence . Number of new cases per time period . Period prevalence . Number of patients with outbreaks during a time period . Varies 2-10%1-3

Period Prevalence 4 STUDY NO AD / NO AD / NO AD / IRRITANT IRRITANT WATER IRRITANT WATER WATER EXPOSURE EXPOSURE EXPOSURE Meding et al. 1990 5-9% 14-23% 34-48%

Nilsson et al. 1986 16% 38% 62-72%

Rystedt et al. 1985 5% 37-50% 60-81%

Hand Eczema Risks 5 . Atopic .Lammintausta et al. 1991 .Coenraads et al. 1998 .Meding et al. 2000 .Meding et al. 2004 .Toledo et al. 2008

Hand Eczema Risks: 6 . Allergic rhinitis/asthma increases risk of hand eczema . But not more than atopic dermatitis4

Hand Eczema Risks: Allergic Rhinitis

7 and Asthma . Female gender increased risk . Coenraads et al. 1983 . Kavli et al. 1984 . Lantinga et al. 1984 . Bryld et al. 2000 . Yngveson et al. 2000 . Meding et al. 2001 . Mortz et al. 2001 . Dickel et al. 2002

Hand Eczema Risks: Female Gender 8 . Meding et al.5 . Wet work in 19-29 year-olds . 37.5% of women occupationally exposed . 18.2% of men . Learbek et al.6 . Private exposures

Why Female Gender ? 9 STUDY TYPE OF STUDY INCIDENCE STUDY POPULATION (PER 100) Lantinga et al. Retrospective General 7.9 1984 Population Uter et al. 1994 Prospective Hairdressers 152

Smit et al. 1994 Prospective Hairdressers 328 Nurses 145 Brisman et al. Retrospective Bakers M: 16.7 F:34.4 1998 Uter et al. 1998 Prospective Office workers 41

Funke et al. 2001 Prospective Industrial Factory 47 Workers

Hand Eczema Risks: Occupation 10 Support Risk Negative Risk Edman et al. Lerbeack et al. Montnemery et al. Berndt et al. Linneberg et al.

Hand Eczema Risks: Smoking 11 ACD7 Delay onset of effective treatment8 Atopic Dermatitis9 Greater area of involved skin10 > 1 year of duration8

Poor Prognosis 12 . Etiology . Morphology . No clear link between morphology and etiology11 . Question the need of morphological classification system

Classification System 13 Irritant Allergic contact dermatitis Atopic dermatitis .80% Idiopathic .20%

Classification System: Etiology 14 . Irritant Contact Dermatitis11 . Most common .Wet work . Water . Mechanic / Machinery oils .Detergents .Tight-fitting gloves .Friction

Classification System: Etiology 15 . Wet hands or glove wearing > 2 cumulative hours daily11,12 . Greater than 20 hand washes daily12

Wet Work 16 . Allergic Contact Dermatitis . Way more common in occupational exposures vs. private exposures (Hobby)11 . “Hand eczema that spreads”13 . Protein Contact Dermatitis . RARE . Latex . Food proteins . Burning, stinging and itching seconds to minutes after contact14 . Systemic Contact Dermatitis . VERY RARE . Specific definition11 . Positive . Ingest an oral version . Vesicular hand/foot rash

Classification System: Etiology 17 . Atopic dermatitis . Other genetic . Filaggrin null mutations15,16 . Twin studies show that MZ twin individuals having a co- twin with hand eczema had an increased risk of hand eczema compared with DZ twins6 . Atopic dermatitis adjusted . Idiopathic CHE . 20%11

Classification System: Etiology 18 . Guidelines of the Danish Contact Dermatitis Group . Chronic dry fissured hand eczema . Vesicular hand eczema . Hyperkeratotic (Tylotic) hand eczema . Interdigital hand eczema . Pulpitis . Nummular hand eczema . Mixed . 50.5% demonstrate multiple morphologies17

Classification System: Morphology 19 Chronic Dry Fissured Hand Eczema 20 Chronic Dry Fissured Hand Eczema 21 Palmoplantar

22 Well-Marginated Palmoplantar Psoriasis 18 23 Abrupt Wrist Cut-off Palmoplantar Psoriasis

24 Micaceous Scale . Frequency based on location19 . 1. Generalized Plaque – 49.3% . 2. Localized Plaque – 16.9% . 3. Guttate – 12.8% . 4. Arthropathic – 7.7% . 5. Palmoplantar – 7.5% . 6. Pustular – 3.1% . 7. Other – 2.7%

Palmoplantar Psoriasis

25 Look Elsewhere . Intermittent20 . Intensely pruritic . Palms/soles, nail, and sides of fingers . Attacks between 1 and 10 months . Two historical descriptions .Pompholyx .

Vesicular Hand Eczema 26 . Frequency of location20 . 1. Hands alone – 46.8% . 2. Feet alone – 24.1% . 3. Hands and feet – 15.6% . 4. Nail apparatus – 13.5%

Vesicular Hand Eczema 27 Anatomic Location20 Fungi Positive

Hands 1.2%

Feet 47.8%

Epidermophyton interdigitale 100% of feet cases

Vesicular Hand Eczema 28 . Lane et al.21 . 25% of any location positive fungal infection . Pitche et al.22 . 10% of any location positive fungal infection . Guillet et al.23 . 15.8% of any location with T. rubrum or candida infection

Vesicular Hand Eczema 29 . Always check the feet . Foot involvement is rare . 47.8% dermatophyte infection

Vesicular Hand Eczema 30 Vesicular Hand Eczema

31 Dyshidrosiform Pattern 32 33 34 Keratolysis Exfoliativa 35 . Presence of erythema . Controversial . Progression of lesions24 . Early stage . Vesicular . Late stage . Chronic dry fissured presentation . Studded with pinpoint necrotic vesicles . Wet glazed look with pinpoint necrotic vesicles

Vesicular Hand Eczema

36 Dyshidrosiform Pattern Vesicular Hand Eczema:

37 Late Stage Dyshidrosiform Pattern . Very rare . Single episode of palms and soles . Vesicular and BULLOUS eruption

Vesicular Hand Eczema: Pompholyx 38 Vesicular Hand Eczema:

39 Pompholyx Dyshidrosiform bullous pemphigoid Herpes gestationis Linear IgA Lymphoma

Autoimmune Blistering Disease and

40 Lymphoma . Localized to palms and soles25 .1. Soles only 47.36% .2. Palms only 31.57% .3. Both soles and palms 21% . Mildly pruritic

Palmoplantar Pustulosis 41 42 43 Middle-aged men NEVER VESICLES

Hyperkeratotic Hand Eczema (Tylotic) 44 Hyperkeratotic Hand Eczema (Tylotic) 45 Palmoplantar Psoriasis 46 Tinea Manuum 47 . Dominant hand . Site for the start of irritant hand dermatitis26,27

Interdigital Hand Eczema 48 Interdigital Hand Eczema 49 Interdigital Hand Eczema 50 Erosio Interdigitale Blastomycetica 51 52 53 54 Pulpitis 55 Pulpitis 56 . Very rare .Must rule out atopic dermatitis .No elevated IgE or eosinophilia . Nummular Atopic Dermatitis (Bologna)

Nummular Hand Eczema 57 Nummular Hand Eczema 58 Any combination of above

Mixed Variety 59 . Systems good for academic pursuit . Pure clinical pictures are less likely . 50.5% demonstrate multiple morphologies17 . Morphology changes frequently clinically and histologically17 . No clear link between morphology and etiology . Johansen et al.28 . Cronin et al.29 . Diepgen et al.30

Problems with Current Classification 60 . Is it an eczematous process? . Acute – vesicles/bullae . Subacute/Chronic – scaling/erythema

Simplification 61 IF ACUTE CHECK THE FEET CHECK THE FEET CHECK THE FEET

Simplification 62 . Hand Eczema . Evaluation Irritant . Do you touch liquids many times a day including water? . Evaluation Atopic . Did you have childhood eczema, allergies or asthma? . Allergic . What do you do for work?

Simplification 63 . Standard Series . Irritant contact . Toledo et al. dermatitis31-33 . Linberg et al. . 21% with positive . Menne et al. patch test34 . Worker’s . 30% relevant Compensation . Nickel (100%) . ACD worse prognosis7

Additional Work Up: Patches 64 . #1 Treatment is the same . #2 Blow them up . Faster clearance at disease onset lowers risk of chronicity43 . #3 And then juice em up . Systemic and topical steroids35 . One episode – 38.4% . Intermittent non-cyclic – 30.8% . Intermittent cyclic-28.5% . Chronic – 2.3% . Patients perceive systemic agents as powerful . #4 Don’t stop treatment if it gets better

Treatment 65 . #5 Shake their hands . #6 What worked before, may not work again . #7 It gets better with time . Period prevalence decreases with aging . 78% of subjects claimed improvement of symptoms over 15 years36

Treatment 66 Study Years to Follow-Up Persistence Agrup et al. 2 years 72% Burrows et al. 10-13 years 79% Reichenberger et al. 15 years 46% Fregert et al. 3 years 68% Gooskes et al. 15 years 55% Lammintausta et al. 5 years 34% Driessen et al. 5 years 50% Keczkes et al. 15 years 69% Latinga et al. 3 years 59% Rystedt et al. 3 years 83% Pryce et al. 2 years 75% Chia et al. 1 year 28% Wall et al. 10 years 55% Halbert et al 10 years 76% Rosen et al 5 years 66% Nethercott et al. 2 years 37% Susitaival et al. 12 years 44%

67 . Decrease number of washes daily (Brancaccio) .“Your hands are broken, if your leg was broken would you still walk on it” .Alcohol based disinfectants are less irritating to the skin than soap and water26 . Apply emollient within 2-3 minutes of wash24 .Greasy as possible .Fragrance free .Apply as many times during day as you like Treatment: Hand Care Instructions 68 . Use gloves when wet work or dirty work . Latex or vinyl . Tight-fitting . Cotton liner .Change when damp

Treatment: Gloves 69 . Which one should I use?17 . Potent 65.5% . Moderate 30.53% . Superpotent 2.3% . Mild 1.67% . How often and for how long?11 . Once daily dosing equal efficacy as twice daily . Two-week intervals . Even switching in the same class can prove to be beneficial (Holland)

First-Line: Topical Steroids 70 . 0.1% vs. mometasone furoate37 . 50% improvement in both groups . vs. mometasone furoate38 . Did not reach statistical significance . Used in combination with steroids . Clear (Cohen) . 1st week: ¾ Steroid Ointment ¼ Tacrolimus . 2nd week: ½ Steroid ointment ½ Tacrolimus . 3rd week: ¼ Steroid ointment ¾ Tacrolimus . 4th week: ALL Tacrolimus . 5th-on: ALL Tacrolimus Fri, Sat, Sun

Alternatives to Topical Steroids 71 . First Blow . Prednisone 40-60mg daily initial dose and taper between 3-4 weeks39 . Intramuscular Kenalog 40-80mg40 . Limit 4 shots per year (Wolverton) . Second Blow . Prednisolone 30mg daily for 3 days at onset of eruptions41 . Prednisone 40-60mg x 1 dose on day 1 of the eruption23

First-Line: Systemic Steroids 72 A Comparison on the Efficacy, Relapse Rate and Side Effects among Three Modalities of Systemic Therapy for Alopecia Areata57 . Triamcinolone acetonide 40mg monthly x 6 . Then 40mg every 6 weeks x 18 months . Total treatment duration = 24 months (2 years) . Total of TEN 40mg injections annually

Routine Intramuscular Steroid 73 A Comparison on the Efficacy, Relapse Rate and Side Effects among Three Modalities of Systemic Corticosteroid Therapy for Alopecia Areata57 . 56 subjects IM Triamcinolone acetonide arm (29 in prednisolone) . 16 dysmenorrhea (vs 3) . 3 abdominal pain (vs 1) . 1 worsening (vs 0) . 5 adrenocortical impairment (vs 2) . Both groups resolved in 2 months without steroid taper

Routine Intramuscular Steroid 74 Twelve-year clinico-therapeutic experience in pemphigus: a retrospective study of 54 cases58 . Intramuscular triamcinolone acetonide was given in cases of poor compliance . 80mg IM on day 0, 4, 7, 28 . 40mg IM every for weeks x 6 doses . Total duration of treatment = 6 months . Total of TEN injections . 1 subject with weight gain . 1 subject with cushingnoid features . Resolved within 4 months without steroid taper

Routine Intramuscular Steroid 75 Triamcinolone acetonide: a new management of noncompliance in nephrotic children59 . 8 monthly doses of IM Triamcinolone acetonide 2mg/kg . Each month dose decreased by 10-20% . Total duration of treatment = 8 months . Total of EIGHT injection . All subjects had decreased longitudinal growth . Normalized

Routine Intramuscular Steroid 76 . S. aureus . Systemic superior to topicals24

Treatment: If infected 77 Botulinum toxin A42 – Left versus right study – Vesicular hand dermatitis only – 100 units plus topical steroids Botulinum toxin43 – Left versus right study – Vesicular hand dermatitis only – 162 units of botox but no steroids

Treatment: If 78 UVA >>> NBUVB >>> UVB52 – Apoptosis of lymphocytes through reactive oxygen species and FAS ligand – Increase in IL-10 inhibition of interferon –gamma. Efficacy PUVA53,54 – Systemic = Topical = Bath – Bath with least side effect • Decreased UVA doses due to uniform absorption • Phototoxicity risk disappears after 2 hours – Sunblock and gloves – High dose UVA-1 • Max single dose of 130J/cm2 • Cumulative dose 1720J/cm2 • As effective as cream puva52 Reduction in pruritus in first week55

Ultraviolet Light 79 Azathioprine 100-150mg daily44 Methotrexate 15-25mg weekly45 Mycophenolate mofetil 2g/day46 Cyclosporine 2.5mg/kg/day47 Etanercept 25mg twice weekly48

Other Systemics 80 Approved Europe – Indicated for chronic hand eczema refractory to topical and systemic steroids – Not for vesicular hand dermatitis Panagonist RXR, RAR Adverse Events – Headache, mucocutaneous dryness, elevated liver enzymes, elevated blood levels, teratogenicity No combination studies

Alitretinoin (9-cis-retinoic acid) 81 30mg daily49 – Median time to clear hands is 12 weeks Placebo, Alitretinoin 10mg, 20mg, 40mg daily doses for 12 weeks50 – 70% reduction in 50% Alitretinoin 10mg, 30mg daily for 24 weeks51 – 100% reduction in 48% – More response with 30mg

Alitretinoin (9-cis-retinoic acid) 82 . Period prevalence . 2-10% . Risk factors . Atopic dermatitis, allergic rhinitis/asthma, occupation, wet irritant exposure . Classification systems . Etiology and morphology . Not practical day-to-day clinic . Differential Diagnosis . Check the feet . First-line therapy options . Blow em up and then juice em up Summary 83 1. Kavli et al. Hand dermatoses in Tromso. Contact Dermatitis. 1984;10:174-177. 2. Coenraads P et al. Prevalence of eczema and other dermatoses of the hands and arms in the Netherlands. Association with age and occupation. Clin Exp Dermatol. 1983;9:495-503. 3. Goh et al. Occupational dermatoses in Singapore. Contact Dermatitis. 1984;11:288-293. 4. Meding et al. Hand eczema in Swedish adults – changes in prevalence between 1983-1996. 5. Meding B etl a. Incidence of Hand Eczema – a population based retrospective study. J Invest Deramtol. 122;873-877.2004. 6. Lerbeak et al. Incidence of hand eczema in a population-based twin cohort: genetic and environmental risk factors. Br J Dermatol.2007;552-557. 7. Cahill et al. The prognosis of occupational contact dermatitis in 2004. Contact Dermatitis. 2004;51:219-226. 8. Veien N et al. Hand eczema:causes, course, and prognosis. Contact Dermatitis. 2008;58:330-4. 9. Toledo et al. Patch testing in children with hand eczema. Contact Dermatitis. 65;213-219. 10.Meding B et al. Fifteen-year follow-up of hand eczema: predictive factors. J Invest Dermatol. 2005;124:893-7. 11. Menne T et al. Hand eczema guidelines based on the Danish guidelines for the diagnosis and treatment of hand eczema. Contact Dermatitis 65;3-12. 12. Coenraads P et al. Risk for hand eczema in employees with past or present atopic dermatitis. Ach Occup Environ Health. 1998;71:7-13. 13. Molin et al. Diagnosing chronic hand eczema by an algorithm: a tool for classification in clinical practice. Clin and Exp Dermatol. 36;595-601. 14. Janssens V et al. Protein contact dermatitis: myth or reality? Br J Dermatol. 1995; 132:1-6. 15.Thyssen J et al. Filaggrin null mutations increase the risk and persistence of hand eczema in subjects with atopic dermatitis: results from a general population study. Br J Dermatol. 2010;115-120. 16.Molin S et al. Filaggrin mutations may confer susceptibility to chronic allergic and irritant hand dermatitis. Br J Deramtol. 2009;801-7. 17.Apfelbacher C et al. CARPE: a registry project of the German Dermatological Society for the characterization and care of chronic hand eczema. JDDG;2011:682-688. 18. Kumar et al. Palmoplantar lesions in psoriasis: a study of 3065 patients. Acta Derm Venerol. 82;192-195. 19. Sampogna et al. Prevalence of symptoms experienced by patients with different clinical types of psoriasis. Br J Dermatol. 2004;151:594-599. 20. Tibor B et al. Pompholyx on the hands and feet. Its etiology, pathogenesis, and specific vaccine therapy. Mycopath et Mycol applicata. 1974;53:25-44. 21. Lane et al. Dermatoses of the hands. JAMA. 128;987-993. 22. Guillet M et al. A-year causative study of pomphylox in 120 patients. Arch Dermatol. 2007;143:12:1504-8. 23. Storrs et al. Acute and recurrent vesicular hand dermatitis not pompholyx or dyshidrosis. Arch Dmeratol. 2007;143-5. 24. Brady M et al. Hands and feet that and peel: dyshidrosis. J Ped Health Care. 1993;7:37-8. 25. Brunasso A et al. Can we really separate plamoplantar pustulosis from psoriasis? JEADV 2010;24:611-624. 26.Kampf G et al. Prevention of irritant contact dermatitis among health care workers by using evidence-based hand hygience practices: a review. Ind health. 2007;645-652. 27.Schwanitz H et al. Interdigital dermatitis; sentinel skin damage in hairdressers. Br J Dermatol. 2000;1011-1012. 28. Johansen et al. Classification of hand eczema: clinical and etiological types. Based on the guideline of the Danish Contact Dermatitis Group. Contact Dermatitis. 65;13-21. 29. Cronin E. Clinical pattern of hand eczema in women. Contact Dermatitis. 1985;13:153-161. 30. Diepgen T etl al. European Environmental contact dermatitis research group. Hand eczema multicentre study of the etiology and morphology of hand eczema. Br J Dermatol. 2009;160:353-358. 31. Veien N et al. Hand eczema: causes, course and prognosis 1. Contact Dermatitis 2008;58:330-334. 32. Lantinga H et al. Prevalence, incidence and course of eczema on the hands and forearms in a sample of the general population. Contact Dermatitis. 1984;10:135-139. 33. Agner T. Hand eczema. Contact Dermatitis. 4th edition. Forsch PI. Berlin. Springer. 2006;pp335-344. 34. Beattie PE et al. Which dhildren should we patch test? Clin Exp Dermatol 2006;32:6-11. 35. Apfelbacher C et al. Occurrence and prognosis of hand eczema in the care industry: results from the PACO follow-up study (PACO II). Contact Dermatitis. 2008;58:322-329. 36. Meding et al. Fifteen-year follow up of hand eczema: persistence and cosequences. Br J Dermatol. 2005;152:975-980. 37. Schnopp C et al. Topical tacrolimus and mometasone furoate in treatment of dyshidrotic palmar eczema: a randomized, observer-blinded trial. J Am Acad Dermatol. 84 2002;46:73-7. 38. Belsito D et al. Multicenter Investigator group: pimecrolimus cream 1%: a potential new treatment for chronic hand dermatitis. Cutis. 2004;73(1):31-8. 39.Wollin U et al. Pharmacotherapy of pompholyx. Exper Opin Pharmaother 2004;5(7)1517-22. 40.Boettget et al. Increased vagal modulation in atopic dermatitis. J Dermatol Sci 2009;53(1):55-9. 41. Veien N. Acute and recurrent vesicular hand dermatitis. Dermatol Clin. 2009;337-353. 42. Wollina et al. Adjuvant botulinum toxin A in dyshidrotic hand eczema: controlled prospective pilot study with left-right comparison. J Eur Acad Dermatol Venereol 2002;16:40-2. 43.Bansal C et al. Novel cutaneous uses for botulinum toxin type A. J Cosmet Dermtol. 2006;5(3):268-72. 44. Sceerri L et al. Azathioprine in dermatological practice: an overview with special emphasis on its use in non-bullous inflammatory dermatoses. Adv Exp Med Biol 1999;455:343-8. 45.Egan et al. Low-dose oral methotrexate treatment for recalcitrant palmoplantar pompholyx. J am Acd Dmeratol. 1999;40(4)612-14. 46. Pickenacker A et al. Dyshidrotic eczema treated with mycophenolate mofetil. Arch Dermatol. 1998;134(3):378-9. 47. Reitamo S et al. Cyclosporin A in the treatment of chronic dermatitis of the hands. Br J Dermatol. 1994;130(1):75-8. 48. Ogden S. Recalcitrant hand pomphylox; variable response to etanercept. Cli and Exp Dermatol. 31; 129-156. 49. Bissonnette R et al. Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema. Br J Dermatol. 2010;162:420-26. 50. Ruzicka et al. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand eczema dermatitis in patient refractory to stand therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004;140(12):1453-9. 51. Ruzicka et al. Efficacy and safety of oral alitretinoin (9-cis-retinoic acid_ in patients with severe chronic hand eczema refractory to topical coriticosteroids: restuls of a randomized double blind, placebo controlled, multicentre trial. Br j Dermatol. 2008;158:808-817. 52. Krutman J. Phototherapy for atopic dermatitis. Clin Exp Deramtol. 2000;25(7):552-8. 53.Grattan C et al. Comparison of topical PUVA with UVA for chronic vesicular hand eczema. Acta Derm Venerol. 1991;71:118-22. 54.Petering H et al. Comparison of locatlized high-dose UVA2 versus topical cream psorlenUVA for treatment of chronic vesicular dyshidrotic eczema. J Am Acad Dermatol. 2004;68-72. 55. UVA1 Irradiation is effective in ttreatment of chronic vesicular dyshidrotic hand eczema. Acta Derm Venerol 56. ansen G. Grenz rays:adequate or antiquated? J Deramtol Surg Oncol 1978;4:627-9. 57. Kurosawa M et al. A comparison of the Efficacy, relapse rate, and side effects among three modalities of systemic corticosteroid therapy for . Der. 2006;212:361-365. 58. Mahajan V et al. Twelve year clinico-therapeutic experience in pemphigus: a retrospective study of 54 cases. In J of Derm. 2005;44:821-827. 59. Ulinknski T et al. Triamcinolone acetonide: a new management of noncompliance in nephortic children. Prediatr Nephrol. 2005;20:759-762.

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