Disorders of

PigmentationBy

Dr.Alaa A. NaifFeb 15, 2015

Causes of hypopigmentationInfection: onchoceciasis, post-kala azar dermal leishmaniasis, , leprosy and pityriasis versicolorPostinflammmatory hypopigmentation: psoroiasisPityriasis alba: mild type of atopic dermatitisGenetic diseases: piebaldism, albinismChemical : rubberPharmacological: topical and intralesional steroidsIdiopathic: vitiligo

Vitiligo

It affect 0.5-2% of general population worldwideAverage age of onset is 20 years but any age can be inflicted by this diseaseCharacterized by absence or decrease of functional melanocytes reflected by absence or decreased DOPA-positive melanocytes

PathogenesisMultifactorial: Genetic + EnvironmentalGenetic:

Susceptibility genes are AIS especially in vitiligo associated with autoimmune diseasesEnvironmental:Autoimmune theory:

Humoral immunity: association with other auto-immune diseases in particular hypo and hyper

thyroidism in addition to Addison’s , DM etc …

Cellular immunity: T cells that infiltrate perilesional epidermis are predominantly CD8 T cells

Intrinsic defects of melanocytes theory: dilatation in rough endoplasmic reticulumDefective free radical defense: H2O2 overproduction in lesional skin leads to oxidative damage of melanocytes

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

of several different pathologic pathways

Clinical PresentationPresent as asymptomatic, non-scaly depigmented macules and patchesAffect face (periorificial), hands, knees, elbows, ankle, nipple, anogenial and and sacrumCan present as isolated localized patch of grey or white hair (poliosis) or as premature diffuse graying of hair ( canities)

Classification

LocalizedFocal

Unilateral(segmental): stop abruptly at the medline

GeneralizedAcrofacial: extremities and faceUniversal: complete or nearly complete

Treatment1)When less than 20% of BSA is affected by

vitiligoTopical corticosteroids: first option

Topical immunosuppressant e.g. tacrolimus Topical pseudocatalase

Surgery: graft or cultured melanocytes for vitiigo unresponsive to topical Rx

2)When more than 20% of BSA is affected by vitiligoNarrowband 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.

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

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 skinEyes may be affected by decreased visual acuity, nystagmus and photophobiaThose patient are at increased risk for skin cancerTreatment is photoprotection, photoprotection and

photoprotection

OCA1A

OCA1B

OCA2(BROWN)

Clinical features Gene defect Type 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

SCC in albinism patient

PiebaldismAutosomal dominant, cc by stable depigmented patches on anterior trunk, mid extremities, central forehead and frontal scalp(white forelock), sparing the backPresent at birthThe involved skin has no melanocytesTreatment: topical steroid and phototherapy is not effective. Auto graft from normal skin is successful

Idiopathic guttate hypomelanosis

It is a very common disorderWell-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 maleEtilology is unknown but sun exposure may play a roleTreatment: cryotherapy and sun protection.

Causes of hyperpigmentation

Infection: Pityriasis versicolorFriction: macular amyloidosisDrug-induced : amiodarone, silver, gold, iron, hydoquinone, minocyclinePostinflammatory hyperpigmentation: lichen planus and fixed drug eruptionPhysical:erythema ab igne which is due to long-term exposure to heat e.g. laptop on the thighsIdiopathic: melasma

MelasmaSynonyms: chloasma, mask of pregnancyIt is most prevalent among young to middle aged womenHispanic, Asian, African or middle eastern descent are inflicted by this disease

Pathogenesis

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

Clinical featuresBrown 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

Treatment

Sun protection , sun protection and sun protection Hydroquinone( tyrosinase inhibitor). Side effects: allergic and irritant contact dermatitis, ochronosisTopical retinoids( inhibitor of tyrosinase transcription)Other tyrosinase inhibitors e.g. kojic acidChemical peels: using salicylic acid and glycolic acidLaser: Q-switched laser and fractional laserDermabrasion

OchronosisThere are two types:

Exogeneous: due to long-term application of hydroquinone, and products containing mercury, resorcinol and phenolRx: cessation of offending drugEndogeneous: due to defect in homogentisic acid oxidase. CC by deposition of pigment in cartilage of ear, nose and on sclera(osler sign) and by arithritisRx:low protein, low tyrosine and low pheylalanine diet

Macular amyloidosis

Pruritic confluent or rippled hyperpigmented macules and patchesMostly involve upper back and forearmsWomen affected more than menlocal friction from nylon brushes, towels and other rough materials contributes to the production of this diseaseTreatment: breaking itch-scratch cycle , stopping friction and use of topical steroids plus keratolytics

Drug Reactions

Epidemiology

The skin is one of the most common targets for adverse drug reactionswomen are more susceptible than menParadoxically, 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

PathogenesisExample The mechanism

IgE-mediated e.g. urticaria 1 .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)

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

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

3 .Literature search e.g medline

Note: Diagnostic or confirmatory test to identify the responsible drug is not available yet

Causative drugs Clinical manifestation Type of drug reaction

SulfonamidesPenicillinCephalosporins

Macules and papules in symmetrical distribution

Exanthematous eruption (the most common drug reaction)

PenicillinsCephalosporinsNSAIDsContrast media

Urticaria, angioedema and anaphylaxis

TMP-SMXNSAIDsTetracyclinesPseudoephedrine

Well-defined erythematous plaque with a dusky hue occur at the same site with every subsequent exposure to the same drug

Fixed drug eruption

AnticonvulsantsSulfonamidesAllopurinol

Maculopapular eruption, facial edema. Lymphadenopathy, visceral involvement and peripheral eosinophilia

DRESS(drug reaction with eosinophilia and systemic symptoms) or hypersensitivity syndrome

AnticonvulsantsSulfonamidesAllopurinol

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)

Treatment

Withdrawal of suspect drug as soon as possibleIf many drugs are incriminated, stop all non-essential drugs

if the suspect drug is essential, substitute with another that does not cross-reactFor mild drug eruption, start topical steroid and systemic antihistaminesStart systemic steroid in case of SJS/TEN and DRESS

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