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HYPERPIGMENTATION DISORDERS

Dr Gita Faghihi DermatologyASSOc. ProfessorIsf.Univ.Med.Sci

Skin colorDepends on:

Amount of :Melanin , Chromophores such as :hemoglobin, carotenoids…

Causes of skin hyperpigmentation

Increase in amount of melanin or number of active melanocytes

deposition of exogenous pigments,…

Classifications of skin hyperpigmentation

(morphologic):

CircumscribedReticularLineardiffuse

Reticular Reticulate acropigmentation of Kitamura

& Dohi Naegeli–Franceschetti–Jadassohn

syndrome Dyskeratosis congenita , .…

Diffuse/Circumscribed Lentigo/Lentiginosis Melasma Erythema dyschromicum perstans Lichen planus pigmentosus Café au lait spot Poikiloderma (Poikiloderma of Civatte),,

(Poikiloderma vasculare atrophicans) Riehl melanosis PIP Acanthosis nigricans Periorbital hyperpigmentation Photoleukomelanodermatitis of Kobori Transient neonatal pustular melanosis

Linear Incontinentia pigmenti Scratch dermatitis(flagellate bleomycin induced) Shiitake mushroom dermatitis

linearity of the lesions is probably related to Blaschko’s lines, which suggests that the predisposition to develop ,,determined during embryogenesis

Others/unclassified(due to drugs, ,exogenous..)

pigments iron: Hemochromatosis • Iron metallic discoloration • Pigmented purpuric dermatosis (Schamberg disease, Majocchi's disease, Gougerot–Blum syndrome, Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis, Lichen aureus, Angioma serpiginosum) • Hemosiderin hyperpigmentation

other metals: Argyria • Chrysiasis • Arsenic poisoning • Lead poisoning • Titanium metallic discoloration

Carotenosis , Tattoo,Tar melanosis

One of the common Diffuse or circumscribed

disorders….

Post inflammatory hyperpigmentationPIH

Postinflammatory hyperpigmentation (PIH)

acquired hypermelanosis …… after cutaneous inflammation or injury ….can arise in all skin types,

But,more frequently affects darker patients,

including : African Americans, Hispanics/Latinos, Asians

Postinflammatory

hyperpigmentationPIH in

Fitzpatrick skin type 4

vs. 6

Note the greater

intensity of pigmentation in darker skin

A wide range of etiologies for PIH:

Acne Infect.(Dermatophytoses, viral

exanthems bacterials.., allergic reactions ( insect bites or a

contact dermatitis, medication-induced PIH from(.. hypersensitivity reactions,

papulosquamous diseases (psoriasis or lichen planus, PR

cutaneous injury from irritants, burns, or cosmetic procedures

Postinflammatory hyperpigmentation after electrodessication for dermatosis papulosa nigra

Acne-induced PIH in a

patient with Fitzpatrick skin type V

Pathophysiology of PIH

In PIH:melanocyte activity ….to

be stimulated by: LTC4, prostaglandins E2 and D2, thromboxane-

2, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, epidermal growth factor, and reactive oxygen species .

First-line therapy (PIH) typically consists of :

Photoprotection (a sunscreen) + topical depigmenting

Topical tyrosinase inhibitors, such as:hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice extracts, can effectively lighten areas of hypermelanosis.

Recent clinical studies have shown that:

topical 5% methimazole,

Topical 2% dioic acid

can successfully treat hyperpigmentation secondary to a variety of etiologies../(PIH).

One of the most common…CIRCUMSCRIBED DISORDERS…

Melasmais an acquired symmetrical pigmentary disorder where confluent grey-brown patches typically appear on the face. %90 of individuals are womenIt is A disease with considerable psychological impactsThe management of melasma is challenging and requires a long-term treatment plan.

factors implicated in the etiopathogenesis of

melasma One of the most important factors in the

development of melasma is ultraviolet exposure from sunlight or other sources

photosensitizing and anticonvulsant medication

mild ovarian or thyroid dysfunction certain cosmetics.

The centrofacial pattern is the most common and involves: the cheeks, nose, forehead, upper lip, and chin.

Wood's lamp examination is of benefit classifiying melasma(epidermal,dermal,mixed/..)

Treatment of melasma, remains a challenge

Kligman and Willis :

hydroquinone (5%) with tretinoin (0.1%) And dexamethasone (0.1%).

Prolonged HQ usage may lead to

untoward effects like

exogenous ochronosis.

In 2006, (FDA) released a statement proposing a ban on all OTC HQ agents based on rodent studies, which suggested that oral HQ may be a carcinogen

so,

Many agents used in the treatment of hyperpigmentation act as tyrosinase inhibitors.

Therapeutic effects:azelaic acid inhibit the energy production and/or DNA synthesis of hyperactive melanocytes,

azelaic acid antityrosinase activity.

azelaic acid This may also account for the beneficial effect on postinflammatory hyperpigmentation. azelaic acid 20% cream twice daily over a period of 12 weeks

Melasma & new treatment modalities:

Tranexamic acid tablets were prescribed at a dosage of 250 mg twice daily for a therapeutic period of 6 months.

75% good to excellent responseNo side effects except hypomenorrhea and mild GI upset in <10%

Other Melasma drugs: Arbutin ,(3-5 %) a herbal agent ,,

higher concentrations of arbutin can lead to a paradoxical hyperpigmentation.

Synthetic forms of arbutin, alpha-arbutin and deoxyarbutin, exhibit greater ability to inhibit tyrosinase

Adding kojic acid, betulinic acid and niacinamideTo arbutin gives better inhibition of Tyrosinase and

higher efficacy

Cont… Melasma treatment

combination of Tretinoin , and kojic acid, and azelaic acid

improve the melasma very effectively .

Other… melasma Therapeutics/ :

There is a lot of documented evidence about efficacy of adapalene gel 0.1%

in melasma

Oral treatments

Dioic acid Resveratrol

Procedures for melasma include:

chemical peel (such as glycolic acid,SA.. …etc..)

microdermabrasion Laser (fractional ,ruby ,low fluence Q-

switch nd:YAG …)

intense pulsed light (IPL)

One of diffuse hyperpig….

ERYTHEMA DYSCHROMICUM PERSTANS

(ashy dermatosis)

ERYTHEMA DYSCHROMICUM PERSTANSMost common in individuals with skin phototypes III–IV(women are more commonly affected) Ashy, gray–brown to blue–gray macules and patches in a symmetric distribution

Lesions favor the neck, trunk and proximal extremities Causes: ■ Genetic susceptibility ■Toxic effects of chemicals such as ammonium nitrate or barium sulphate ■ worm infestation ■ Viral infections ■ Adverse effect of drugs and medications

Pigmentary incontinence vacuolar degeneration

(ashy dermatosis)

Erythema dyschromicum perstans

(also known as "Ashy dermatosis," ) is a skin condition with age

of onset almost always before 40 years old

characterized by skin lesions that are usually symmetrical and generalized

A consistently effective treatment is not currently availableBut some case series responded to oral corticosteroids

Treatment/ ashy dermatosis ...

The use of narrow-band UVB phototherapy has shown success in a few patients

A low-potency topical steroid applied twice a day to the affected areas may be used, with or without a 4% hydroquinone cream for the hyperpigmentation

A patient from Turkey was described to have responded remarkably well to treatment with dapsone

Diff. diagnosis , for ashy dermatosis

Lichen planus pigmentosus

LICHEN PLANUS PIGMENTOSUS

Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus that favors individuals with skin phototypes III–V, including those from India Latin America and the Middle East.

LPP usually has its onset during the third or fourth decade of life; it presents as oval or round, brown, gray–brown or dark brown macules and patches in either sun-exposed areas (especially the forehead, temples and neck) or intertriginous zones.

There may be no associated symptoms versus mild pruritus or burning, and, in contrast to some cases of EDP, early lesions do not have an erythematous border

Gray–brown to dark brown macules and patches in either a photodistribution or an inverse (intertriginous) pattern

Tacrolimus (protopic ) ointment is effective in

LPP

One common Cicumscribed,,retic/

hyperpig/

Amyloidosis a spectrum of disorders characterized by the deposition of amyloid within the skin and other tissues .

Primary (localized) cutaneous amyloidosis is subdivided into three major forms– macular, lichenoid and nodular

the first two are associated with hyperpigmentation.

The most common locations are the upper back (macular amyloidosis) and the extensor surface of the lower extremities (lichen amyloidosis). Areas of involvement are often pruritic, and because rubbing plays a key role in the production of lesions, there is a characteristic rippled pattern with parallel bands or ridges of hyperpigmentation.

Histologically, melanophages as well as amyloid deposits that stain positively with antikeratin antibodies are seen within the upper dermis.

chronic pruritic hyperpigmented patches on upper back esp/. in adult

women

Diagnosis:Primary cutan .Amyloido/

congo red staining under polarized light forms a very sensitive and definitive

method for confirmation.

treatment modalities in macular amyloidosis and lichen amyloidosis

relief of pruritus. •Sedating antihistamines have been found to be moderately effective.

Topical dimethyl sulfoxide (DMSO), a chemical solvent

intralesional steroids are beneficial if combined with other modalities.

Treatment with ultraviolet B (UV-B) light can provide symptomatic relief.

improvement of lichen amyloidosis with pulsed dye laser therapy595-

nm-. Both pruritus and the papular eruption of lichen amyloidosis

improved

Reticulate acropigmentation of

Kitamura

pigmented macules on the volar and dorsal aspects of the hands and feet,

lineaa palmar pits

Reticulate acropigmentation of Kitamura

usually autosomal-dominant fashion

punctate, irregular, atrophic, brown macules involving the dorsa of the hands and feet, the dorsa of the kneesthe extensor surface of the neck, both axillary regions, the abdominal skin andthe inguinal region,

Treatment: Reticulate acropigmentation of

Kitamura

Most treatments attempted have been unsuccessful,

but an attempt to treat the disease with 20 % azelaic acid gave significant improvement

Er-YAG laser treatment

Reticulate acropigmentation of Dohi (RAD)

is characterized by the presence of hyperpigmented and hypopigmented pinpoint or pea-sized macules over the dorsa of the hands and feet and occasionally on the arms and legs

Naegeli-Franceschetti-Jadassohn (NFJ)

syndrome

is a reticulate pigmentary disorder and a type of Ectoderm/ dysplasia/

syn..

Naegeli-Franceschetti-Jadassohn (NFJ) syndrome

is a rare autosomal dominant form of ectodermal dysplasia that affects the skin, sweat glands, teeth and PPK .

Hypohidrosis

dental anomalies

PPK

No treatment is effective in Naegeli-Franceschetti-Jadassohn (NFJ) syndrome. As with other ectodermal dysplasias, exposure to heat should be limited and sufficient hydration is recommended. Tooth care to prevent early caries is indicated.

Doxycycline has been found to interfere with tumor (TNF-alpha)–mediated signaling and apoptosis may have a role in future treatment

Dyskeratosis congenita

another retic/hyperpig,/

Dyskeratosis congenita Affected individuals often

have fingernails and toenails that grow poorly or are abnormally shaped.

They also often have changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as "lacy."

White patches inside the mouth (oral leukoplakia

Dyskeratosis congenita

major consequence being: bone marrow failure and/at increased

risk of developing leukemia

People with dyskeratosis congenita are also In addition have a higher risk of other cancers, especially head, neck, anus, or genitals

Poikiloderma of Civatte

is a cutaneous condition and refers to : Reticulated red-brown patches with

telangiectasias

Poikiloderma of Civatte refers to erythema associated with a mottled pigmentation seen on the cheeks & sides of the neck

No specific medical treatment exists for poikiloderma of Civatte

Erythromelanosis Follicularis of Face and

Neck

reddish-brown pigmentation and telangiectasis surmounted with pale, tiny follicular papules involving periauricular area

Linear hyperpig disorders

Linear and whorled nevoid hypermelanosis(LWNH)

Reticulate and zosteriform (“Zebra-like”) hyperpigmentation, in whorls and streaks

is a disorder of pigmentation that develops within a few weeks of birth and progresses for one to two years before stabilizing.

Treatment ((LWNH)) : chemical peel Q-S laser

A little help in some patients but, a proven treatment approach for LWNH does not exist.

Epidermal naevi in blaschko

lines

Incontinentia pIgmenti(x-linked dominant)

typical neonatal vesicular rash with eosinophilia;

typical blaschkoid hyperpigmentation

Cutaneous findings are the most common manifestation of IP

and usually represent the presenting signs. They are divided into four overlapping stages: (1) vesiculobullous, which favors the extremities during

the first few months of life (but occasionally recurs during childhood in association with a febrile illness);

(2) verrucous, which favors the distal extremities in patients one to six months of age (and sometimes adolescents);

(3) hyperpigmented, which favors the trunk and intertriginous sites from three months of age through adolescence; and

(4) hypopigmented/atrophic, which affects the calves in adolescents and adults

The hyperpigmentation

of the third stage(IP) is seen in just about

all patients,

beginning at 3-6 months of life.

In contrast to the vesicular and

verrucous lesions, the pigmentary

changes are generally truncal in distribution and not

proceeded by inflammatory

changes.

IP*(assoc.) Hyperpigmented lines are

fading in adolescence linear, atrophic hairless

lesions.

dental anomalies,

alopecia, wooly hair, and

abnormal nails Seizure or MR Retinal /ophthalmic

disorders(blindness..)

Circumscribed hyperpig.,disorders

Laugier-Hunziker Syndrome:

An Uncommon Cause of Oral Pigmentation ….

Laugier-Hunziker syndrome

is a rare acquired macular hyperpigmentation of oral mucosa and lips frequently associated with longitudinal pigmentation of the nails

The pathogenesis is unknown, but no systemic involvement no family history of the disease or no intestinal polyposis, or

no malignant predisposition has been described

Diffuse macular brown pigmentation on the

vermilion of the lower lip.

Longitudinal pigmented band on the right great toenail.

Laugier-Hunziker syndrome flat brown marks on the lips and inside the mouth, and frequently brown stripes on the nails.

Diffuse and discrete. Hyperpig. Dis./

Urticaria pigmentosa

Rubbing the skin lesions causes a hive-like bump. Younger children may develop fluid-filled blisterThe face may also flushed.

In severe cases, the following symptoms :

•Diarrhea

•Fainting

•Headache

• tachycardia

usually affects the neck, arms, legs and trunk of children and young adults. The rash consists of reddish-brown spots

The exact cause of this uncommon disease is unknown but recent research suggests genetic change in a protein (called c-kit) on the surface of mast cells may result in the abnormal proliferation of these cells.

Variety of factors can cause or worsen the symptoms of urticaria pigmentosa:

Physical stimuli such as heat, friction, and excessive exercise

Bacterial toxins Venom Eye drops containing dextran Alcohol Morphine Emotional stress

Cetirizineloratadinefexofenadine

more superior to first generations

Mast cell stabilizers

calcium channel blockers

Treatment of mastocytosis

Circumscribed or diffuse/ pig. lesions

Lentigo solaris

Lentiginessun-exposed areas

Mucosal lentigines (also known as "Labial, penile, and vulvar melanosis," and "Melanotic

macules")

is a cutaneous condition characterized by :light brown macules on mucosal surfaces

Lentiginosis refers

to the

presence of lentigines in large numbers or in a distinctive

configuration

LEOPARD syndromeLEOPARD syndrome Lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness syndrome)

(ie, multiple lentigines syndrome) is a complex dysmorphogenetic disorder that is transmitted as an autosomal-dominant trait

Café au lait macules(CALM)

pigmented birthmarks The name café au lait is French for

"coffee with milk" and refers to their light-brown color

They can be treated with

Q -Switch lasers

Oculodermal melanocytosis(Nevus of Ota )

Nevus of Ota

Epidemiology

is more common in Japanese, in women (9 times) with onset either in the perinatal period or around puberty

Etiology

genetic factors are thought to be important but familial cases are rare.

Pathogenesis

represents aborted embryonic migration of melanocytes from neural crest to epidermis. Late pubertal onset is explained by pigmentation of the amelanotic nevoid cells present at birth by adolescent spurt of sex hormones.

Clinical features

is characterized by speckled or mottled coalescing blue-grey pigmentation of the area supplied by ophthalmic and maxillary divisions of trigeminal nerve. It is usually unilateral (90%).

topical therapy is of no valueQ-switch lasers

The sclera is involved in two-thirds of cases (causing an increased risk of glaucoma).

Crops of red-brown flat patches with cayenne pepper spots on their borders appear for no apparent reason. most common on the lower

legs,

Schamberg disease

Progressive pigmented

Purpuric dermatoses.

Schamberg”s

Topical steroids can

be helpful for itching but rarely clear

the capillaritis. Currently available lasers are not particularly helpful for pigmented purpuric dermatoses

Treatment(cont..d)

(pentoxifylline) circulation,

Vitamins (Vitamin C 500mg twice daily )

Bioflavonoid (Complex with Rutin)

Avitaminosis esp. Vit. B12 Def.

Caused hyperpig. of skinresolves after Vit . Supplement

In patients with vitamin B12 deficiency, the following skin lesions are reported:

skin hyperpigmentation, vitiligo, hair changes, recurrent angular stomatitis

Hyperpigmentation of the extremitiesespecially over the dorsum of the hands and feet, with accentuation over the interphalangeal joints and terminal phalanges

Drug induced reactions

Drug-induced pigmentary abnormalities classified into 3 groups,

hyperpigmentation/melanosis

hypopigmentation/leukoderma and

dyspigmentation or occurrence of unusual skin color.

DRUG-INDUCED ‘HYPERPIGMENTATION’

Although several classes of drugs are known to induce ‘hyperpigmentation’, the most common are: minocycline, phenothiazines antimalarials, chemotherapeutic agents Zidovudine Amiodarone

mucosal pigmentations and Longitudinal or horizontal melanonychia may also be present

pigmentation usually resolves with discontinuation of the offending drug,

but the course may be prolonged

Photoleukomelanodermatitis of Kobori thiazides tetracyclines

followed by exposure to sunlightEdematous erythema with slight itching appeared on the sun-exposed areas ,the cutaneous lesions almost disappeared after drug stop

but pigmentations and depigmentations develop in spots in sun-exposed areas.

Photopatch and oral challenge tests were positive.

Summary:Facial melanoses (FM) are a common presentation in dermatologic patients, causing cosmetic disfigurement with considerable psychological impact. Some of the well defined causes of FM include melasma, Riehl's melanosis, Lichen planus pigmentosus, and poikiloderma of Civatte. But there is considerable overlap in features amongst the clinical entities. Etiology in most of the causes is unknown, but some factors such as UV radiation in melasma, exposure to chemicals in EDP, exposure to allergens in Riehl's melanosis are implicated. Diagnosis is generally based on clinical features. The treatment of FM includes removal of aggravating factors, vigorous photoprotection, and some form of active pigment reduction either with topical agents or physical modes of treatment. Topical agents include hydroquinone (HQ), which is the most commonly used agent, often in combination with retinoic acid, corticosteroids, azelaic acid, kojic acid, and glycolic acid. Chemical peels are important modalities of physical therapy, other forms include lasers and dermabrasion.

The end

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