1. Disorders of Pigmentation By Dr.Alaa A. Naif Feb 15, 2015

2. Causes of hypopigmentation Infection: onchoceciasis, post-kala azar dermal leishmaniasis,, leprosy and pityriasis versicolor Postinflammmatory hypopigmentation: psoroiasis Pityriasis alba: mild type of atopic dermatitis Genetic diseases: piebaldism, albinism Chemical : rubber Pharmacological: topical and intralesional steroids Idiopathic: vitiligo

3. Vitiligo It affect 0.5-2% of general population worldwide Average age of onset is 20 years but any age can be inflicted by this disease Characterized by absence or decrease of functional melanocytes reflected by absence or decreased DOPA-positive melanocytes

4. Pathogenesis Multifactorial: Genetic + Environmental Genetic: Susceptibility genes are AIS especially in vitiligo associated with autoimmune diseases Environmental: Autoimmune theory: Humoral immunity: association with other auto- immune diseases in particular hypo and hyper thyroidism in addition to Addison’s, DM etc…

5. Cellular immunity: T cells that infiltrate perilesional epidermis are predominantly CD8 T cells Intrinsic defects of melanocytes theory: dilatation in rough endoplasmic reticulum Defective free radical defense: H2O2 overproduction in lesional skin leads to oxidative damage of melanocytes

6. Neural theory:especially in segmental vitiligo. They believe that neuropeptides released from nerve endings cause decreased melanin productio Viral theory:Cytomegalovirus DNA has been identified in skin biopsy specimen of some patients with vitiligo, causing damage to melanocytes Convergence theory: available data suggest that vitiligo is multifactorial and may be the end result of several different pathologic pathways

7. Clinical Presentation Present as asymptomatic, non-scaly depigmented macules and patches Affect face (periorificial), hands, knees, elbows, ankle, nipple, anogenial and and sacrum Can present as isolated localized patch of grey or white hair (poliosis) or as premature diffuse graying of hair ( canities)

10. Classification Localized Focal Unilateral(segmental): stop abruptly at the medline Generalized Acrofacial: extremities and face Universal: complete or nearly complete

18. Treatment 1)When less than 20% of BSA is affected by vitiligo Topical corticosteroids: first option Topical immunosuppressant e.g. tacrolimus Topical pseudocatalase Surgery: graft or cultured melanocytes for vitiigo unresponsive to topical Rx

20. 2)When more than 20% of BSA is affected by vitiligo Narrowband UVB(311 nm): first choice Psoralen plus phototherapy(PUVA): psoralen can e applied topically(topical PUVA) or oral (oral PUVA) followed by exposure to artificial UV light or natural sunlight.

21. Permanent depigmentation: e.g. monobenzyl ether of hydroquinone is used when vitiligo involve more than 50% of BSA and unresponsive to phototherapy Others: systemic anti-oxidant and excimer laser

26. Oculocutaneous albinism Autosomal recessive group of diseases characterized by diffuse pigmentary dilution due to partial or total absence of mealnin in skin, hair follicles and eyes despite the normal number of melanocytes in skin Eyes may be affected by decreased visual acuity, nystagmus and photophobia Those patient are at increased risk for skin cancer Treatment is photoprotection, photoprotection and photoprotection

27. OCA1A

28. OCA1B

29. OCA2(BROWN)

30. Clinical featuresGene defectType of albinism White skin, white hair and blue eyes (some are blind) Develop some pigmentation of hair and skin with age (yellow OCA) Tyrosinase(complete absence of activity) Tyrosinase (Partial absence of activity) OCA1A OCA1B Skin and hair are light brown (brown OCA) OCA2

32. SCC in albinism patient

33. Piebaldism Autosomal dominant, cc by stable depigmented patches on anterior trunk, mid extremities, central forehead and frontal scalp(white forelock), sparing the back Present at birth The involved skin has no melanocytes Treatment: topical steroid and phototherapy is not effective. Auto graft from normal skin is successful

37. Idiopathic guttate hypomelanosis It is a very common disorder Well-defined asymptomatic porcelain-white macules that don’t change in size and don’t repigment Mostly involves forearms and legs (photoexposed areas) Affect dark skinned people more than caucasian Incidence increase with age and female are affected more than male Etilology is unknown but sun exposure may play a role Treatment: cryotherapy and sun protection.

47. Causes of hyperpigmentation Infection: Pityriasis versicolor Friction: macular amyloidosis Drug-induced : amiodarone, silver, gold, iron, hydoquinone, minocycline Postinflammatory hyperpigmentation: lichen planus and fixed drug eruption Physical:erythema ab igne which is due to long- term exposure to heat e.g. laptop on the thighs Idiopathic: melasma

48. Melasma Synonyms: chloasma, mask of pregnancy It is most prevalent among young to middle aged women Hispanic, Asian, African or middle eastern descent are inflicted by this disease

49. Pathogenesis Exposure to UV : fading of lesion in winter, involvement of sun-exposed areas and sparing of philtrum Genetic/ethnic predisposition : Mostly it is related to darker skin type Hormones: OCP, pregnancy (appearnace or exacerbation) Autoimmune thyroid diseases

50. Clinical features Brown or gray patches on the face, but may affect extensor forearm and central upper chest May lighten or disappear after delivery in light skinned women but may persist in dark skinned Using Wood’s lamp, melasma is subdivided into epidermal( the lesion is accentuated), dermal (the lesion blend with the surrounding) and mixed

52. Treatment Sun protection, sun protection and sun protection Hydroquinone( tyrosinase inhibitor). Side effects: allergic and irritant contact dermatitis, ochronosis Topical retinoids( inhibitor of tyrosinase transcription) Other tyrosinase inhibitors e.g. kojic acid Chemical peels: using salicylic acid and glycolic acid Laser: Q-switched laser and fractional laser Dermabrasion

53. Ochronosis There are two types: Exogeneous: due to long-term application of hydroquinone, and products containing mercury, resorcinol and phenol Rx: cessation of offending drug Endogeneous: due to defect in homogentisic acid oxidase. CC by deposition of pigment in cartilage of ear, nose and on sclera(osler sign) and by arithritis Rx:low protein, low tyrosine and low pheylalanine diet

56. Macular amyloidosis Pruritic confluent or rippled hyperpigmented macules and patches Mostly involve upper back and forearms Women affected more than men local friction from nylon brushes, towels and other rough materials contributes to the production of this disease Treatment: breaking itch-scratch cycle, stopping friction and use of topical steroids plus keratolytics

62. Drug Reactions

63. Epidemiology The skin is one of the most common targets for adverse drug reactions women are more susceptible than men Paradoxically, the incidence of most immunologically mediated drug eruptions is increased in the setting of immunosuppression; for example, in patients with AIDS The incidence of adverse reactions also increases with the age of the patient

64. Pathogenesis ExampleThe mechanism IgE-mediated e.g. urticaria1. Immunological mechanisms (unpredictable) Phamacological side effects e.g. Chemothearapy cause hair loss that cannot be seperated from the desirable action of this drug 2. Non-immunological mechanisms (predictable) Stevens- Johnson syndrome/Toxic epidermal necrolysis 3. Idiosyncratic (unpredictable and can not be explained on the basis of pharmacological properties of drug)

65. APPROACH TO DETERMINE THE CAUSE OF A DRUG ERUPTION 1. Clinical characteristics: Type of the lesion e.g. maculopapular lesions in morbilliform drug eruption, Distribution of lesions e.g. recurrence of the lesion at exactly the same site with each exposure to the same drug in fixed drug eruption, Mucous membrane involvement e.g. in SJS/TEN Associated features such as fever, lymphadenopathy and visceral involement e.g. all are manifested in DRESS

66. 2. Chronological factors: Document all drugs to which the patient has been exposed and the dates of administration Date of eruption Time interval between drug introduction and skin eruption because most of drug eruption occurs within 1-3 weeks after initiation of new drug Response to removal of the suspected agent Response to rechallenge(re-administration of drug) such as in fixed drug eruption which is not life- threatenening

67. 3. Literature search e.g medline Note: Diagnostic or confirmatory test to identify the responsible drug is not available yet

68. Causative drugsClinical manifestationType of drug reaction Sulfonamides Penicillin Cephalosporins Macules and papules in symmetrical distribution Exanthematous eruption (the most common drug reaction) Penicillins Cephalosporins NSAIDs Contrast media Urticaria, angioedema and anaphylaxis TMP-SMX NSAIDs Tetracyclines Pseudoephedrine Well-defined erythematous plaque with a dusky hue occur at the same site with every subsequent exposure to the same drug Fixed drug eruption Anticonvulsants Sulfonamides Allopurinol Maculopapular eruption, facial edema. Lymphadenopathy, visceral involvement and peripheral eosinophilia DRESS(drug reaction with eosinophilia and systemic symptoms) or hypersensitivity syndrome Anticonvulsants Sulfonamides Allopurinol Maculopaular eruption, severe mucous membrane invlovement e.g. mouth, eyes, genitalia and positive Nikolsky sign (sloughing of skin on pressure by finger) SJS/TEN( Stevens-Johnson syndrome/ Toxic epidermal necrolysis)

69. Treatment Withdrawal of suspect drug as soon as possible If many drugs are incriminated, stop all non- essential drugs if the suspect drug is essential, substitute with another that does not cross-react For mild drug eruption, start topical steroid and systemic antihistamines Start systemic steroid in case of SJS/TEN and DRESS

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