Disorders of Pigmentation

Disorders

of
Pigmentation
By
Dr.Alaa A. Al-Sahlany
May 13, 2020

Causes of hypopigmentation

Infection: 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

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 melanocytes reflected by absence or decreased DOPA-positive melanocytes

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…

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 lead to oxidative damage of melanocytes

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

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)

Classification

Localized:

Unilateral(segmental): stop abruptly at the medline

Acrofacial: extremities and face

Generalized:

Universal: complete or nearly complete

Treatment

If less than 20% of BSA is affected by vitiligo:

Topical corticosteroids: first option

Topical immunosuppressant e.g. tacrolimus and topical pseudocatalase

Surgery: punch graft, suction blister graft, cultured melanocytes for vitiligo unresponsive to topical Rx

If more than 20% of BSA is affected by vitiligo:

Narrowband UVB(311 nm): first choice


Psoralen plus phototherapy(PUVA): psoralen can be applied topically(topical PUVA) or oral (oral PUVA) followed by exposure to artificial UV light or natural sunlight.

Excimer laser

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, topical pseudocatalase

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

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

Bronze skin color , red hair (rufous albinism)

OCA3

Decreased visual acuity, phtophobia and nystagmus. Skin is normal

OA1

OCA1A

OCA1B

OCA2(BROWN)

Temperature-sensitive albinism

SCC in albinism patient

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

Causes of hyperpigmentation

Infection: Pityriasis versicolor

Friction: macular amyloidosis

Drug-induced : amiodarone, silver, gold, 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

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


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

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







Treatment
Sun protection , sun protection and sun protection

Hydroquinonen( tyrosinase inhibitor). Side effects: allergic and irritant contact dermatitis, ochronosis

Kojic acid (tyrosinase inhibitor)

Azelaic acid (tyrosinase inhibitor)

Others: Chemical peels e.g. using salicylic acid and glycolic acid, Laser, Dermabrasion

Ochronosis
There are two types:
(1)Exogeneous: due to long-term application of hydroquinone, and products containing mercury, resorcinol and phenol
Rx: cessation of offending drug

(2) 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

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

Drug Reactions

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

Pathogenesis
Example
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 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

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
Sulfonamides
PenicillinCephalosporins
Macules and papules in symmetrical distribution which looks like a measle
Morbillliform eruption (the most common drug reaction)
PenicillinsCephalosporinsNSAIDsContrast media


Urticaria, angioedema and anaphylaxis
TMP-SMXNSAIDsTetracyclinesPseudoephedrine
Erythematous plaque with a dusky hue occur at the same site with every subsequent exposure to the same drug
Fixed drug eruption
AnticonvulsantsSulfonamidesAllopurinol
Morbilliform eruption, facial edema, fever, lymphadenopathy, visceral involvement in addition to peripheral eosinophilia
DRESS (drug reaction with eosinophilia and systemic symptoms) or hypersensitivity syndrome
AnticonvulsantsSulfonamidesAllopurinol
Morbillform 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 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

For severe drug erupton such as SJS/TEN and DRESS, start systemic steroid

Thanks

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Watching