DOI: 10.1111/j.1610-0387.2009.07137.

x Academy 187

CME

Disorders of Pigmentation
Susanna K. Fistarol, Peter H. Itin
Department of Dermatology, Basel University Hospital, Switzerland

Section Editor
Prof. Dr. Jan C. Simon,
JDDG; 2010 • 8:187–202 Submitted: 9. 2. 2009 | Accepted: 21. 4. 2009 Leipzig

Keywords Summary
• disorder of pigmentation Skin color is highly individual and the variations are controlled by numerous
• hypopigmentation genes. The different skin colors result from the size and number of
• hyperpigmentation melanosomes and do not mirror the amount of melanocytes. Disorders of pig-
• genodermatosis mentation can result from migration abnormalities of melanocytes from the
• melanocytes neural crest to the skin during embryogenesis. In addition, impairment of
• melanosomes melanosome transfer to the surrounding keratinocytes, an alteration in
melanin synthesis and a defective degradation or removal of melanin may lead
to abnormal skin pigmentation. Immunologic or toxic mediated destructions
of melanocytes can end in pigmentation disorders. Disorders of pigmentation
are classified in hypo- or hyperpigmentation which can occur as a genetic or
acquired disease. They can manifest locally or diffuse. Congenital hypopigmen-
tation can be restricted to the skin as in piebaldism or they represent a sys-
temic disease as in Menkes disease or phenylketonuria. Localized hypo- or
hyperpigmentation in children may serve as markers for systemic diseases.
Ash-leaf hypopigmentation are characteristic for tuberous sclerosis and more
than 5 café-au-lait spots suggest neurofibromatosis 1 (von Recklinghausen dis-
ease). The most common autoimmune-induced depigmentation is vitiligo.
Generalized hyperpigmentation only rarely reflects a primary genetic disorder
but is most often from acquired diseases as in Addison disease, secondary
hemochromatosis or primary biliary cirrhosis. Treatment of pigmentation disor-
ders are based on a diagnosis which sometimes allow a specific intervention.
Cosmetically acceptable results are difficult to obtain.

Introduction
Definition and classification
The normal color of the skin is primarily determined by its pigment content. The
most important pigments for skin color are melanin, oxygenated and reduced hemo-
globin, and carotene [1]. Other factors that influence the appearance and color of the
skin include epidermal thickness and vascular supply, including the number, caliber,
and reactivity of blood vessels in the dermis [2].
Melanin is produced by epidermal melanocytes. Melanocytes arise from the neural crest
during embryonic development and are located in the basal layer of the epidermis [3].
Melanocytes contain specialized organelles that synthesize melanin, which is then re-
leased by the dendrites as mature melanosomes to an average of 36 keratinocytes. Syn-
thesis of melanin from tyrosine is catalyzed by the enzyme tyrosinase. Tyrosine is first
converted into dopa and then dopaquinone. Human skin contains three different types
of melanin: eumelanin which is brown or black, pheomelanin which is red or yellow, and

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The level of melanin production is
determined by the gene for the
melanocortin receptor 1(MC1R)
Variations in individual skin color and
between people of various ethnicities
are not due to the number of
melanocytes, but rather are caused by
the number and size of melanosomes.
Hypopigmentation results from a re-
duction in the number of melanocytes
and/or mature melanosomes or from
abnormal transfer of mature
melanosomes to neighboring ker-
atinocytes.
Hyperpigmentation is due to in-
creased melanin production caused
by increased melanocyte and tyrosi-
nase activity, as well as delayed break-
down and removal of melanin
Pigmentation anomalies may be
localized or diffuse, congenital or
acquired, and may or may not be
accompanied by systemic symptoms.
Pigmentation anomalies should be
classified using a specific algorithm.
The algorithm presented here includes
the pattern of pigmentation, age of
onset, and accompanying symptoms.
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trichromes, which are present in various chemically well-defined variants. The level of
melanin production is determined by the gene for the melanocortin receptor 1(MC1R)
[4]. In humans MC1R is located on chromosome 16, gene locus q24.3. MC1R is a
coded transmembrane G-protein coupled receptor which is expressed in melanocytes
and controls tanning (sensitivity to light exposure and sun burn), influences skin and
hair color, and partly determines individual risk of melanoma. Variations in skin color
from one person to the next and between people of various ethnicities are determined by
the number and size of mature melanosomes and not by the number of melanocytes.
The ratio of melanocytes to basal cells is 1 : 4 to 1 : 9 depending on the region of the
body, but irrespective of ethnic origin. The face has the highest density of melanocytes at
2 900 ± 249/mm2, while the upper arm has the lowest at 1 100 ± 215/mm2.
Melanin synthesis is influenced by genetic factors and varies greatly among individu-
als, families, and ethnicities. Other factors include exposure to UV light, hormonal
influences, and biochemical substances. Hypophyseal hormones such as melanocyte-
stimulating hormone (MSH, melatonin), ␤-lipotropin, and to a lesser extent adreno-
corticotropic hormone (ACTH) all have melanocyte-stimulating activity. At high
doses melatonin produces a dirty brown-gray skin color.
Hypopigmentation results from a reduction in the number of melanocytes and/or ma-
ture melanosomes or from abnormal transfer of mature melanosomes to neighboring
keratinocytes. Hypopigmentation may be diffuse or localized, congenital or acquired,
and is associated with a specific distribution pattern. Hyperpigmentation is due to in-
creased melanin production caused by increased melanocyte and tyrosinase activity, as
well as delayed breakdown and removal of melanin (metastasizing melanoma, Sézary
syndrome, kala-azar, Addison disease). If there is extensive involvement of the skin the
condition is known as melanoderma. Acquired pigmentary disorders due to chemical
or physical causes are referred to as leukoderma or melanoderma.
Diagnostic procedures
There are more than 4,000 different known diseases of the skin. Many of these disor-
ders are associated with a change in skin color. Diagnosis is based on expert opinion
and on clinical experience. As yet, an evidence-based validation of these diagnostic
measures is still lacking.
It would be all but impossible to maintain sufficient knowledge of all possible disease
entities at one time. Following a systematic diagnostic procedure is essential. Patho-
logical changes in pigmentation may be analyzed with the aid of an algorithm which
provides a rough classification of the disease (Figure 1). The classification is based on
the patient’s medical history and clinical physical examination of the entire body.
Only then should additional – and sometimes costly - diagnostic procedures be un-
dertaken.
Patient history
Information should be elicited from the patient on family history, onset, and devel-
opment of pigmentation changes. Patients should also be asked about any related im-
pact on overall health as well as any pathologies involving other organs [5, 6]. A med-
ication history should also be taken and should include occupational contacts with
solvents which can lead to hyperpigmentation or – as a result of toxic effects on
melanocytes - hypopigmentation (Table 1).
Clinical examination
The presence of hyper- or hypopigmentation, and whether it is congenital or ac-
quired, diffuse or localized, is confirmed by the patient’s medical history and the re-
sults of clinical examination. Any accompanying disorders, especially signs of neu-
roectodermal disorders, must also be noted. If the pigmentary changes are acquired,
the age of onset of disease is an important factor. Bolognia has recommended using
three broad age categories: birth/infancy, childhood, and adulthood [7].
Hypopigmentation
Hypopigmentation may be classified by age of onset and underlying pathogenetic mech-
anisms. Any extracutaneous accompanying disease is also an important factor for diag-
nosis. The various patterns include diffuse, localized, linear and patchy involvement.
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Pigmentation anomalies

Hypo-/hyperpigmentation

Congenital Acquired

Diffuse Diffuse

Localized Localized

Along lines of Blaschko Along lines of Blaschko

Isolated Isolated

Accompanying disease Accompanying disease

Segmental, dermatome Segmental, dermatome

Isolated Isolated

Accompanying disease Accompanying disease

Aggregated, quadrant-like,
Phylloid checkerboard pattern
bathing-suit appearance

Figure 1: Algorithm for evaluating disorders of pigmentation. Based on Bolognia J (1999) A clinical approach to leukoderma. Int.J.Dermatol. 38:568–572.

Diffuse hypopigmentation Table 1: Patient history in disor-

at birth/early childhood
ders of pigmentation.

Eyes, skin, hair Skin and/or hair • Familial incidence

• Onset and development
• Medication use
Piebaldism, Oculocutaneous Phenylketonuria, Menkes Griscelli Elejalde Malnutrition Ectodermal
histidinemia, dysplasia
• Contact with solvents
Waardenburg albinism
homocystinuria • Accompanying symptoms

Type 1 Type 2 Type 3 Hermansky-Pudlak Chédiak-Higashi

Angelman Prader-Willi

Figure 2: Algorithm for differential diagnosis of diffuse hypopigmentation during childhood. Based
on Bolognia J (1999) A clinical approach to leukoderma. Int.J.Dermatol. 38:568–572.

Hypopigmentation at birth or in infancy with involvement of the skin and hair

and with or without ocular involvement (Figure 2)
In diffuse hypopigmentation which is present at birth or manifests during early child-
hood, various organs which harbor melanocytes may be involved. These forms of hy-
popigmentation may be divided clinically into two groups: one in which the skin,
hair, and eyes are affected, and a second group in which only the skin and/or hair are
involved (Figure 2). In regard to pathogenesis, congenital hypopigmentation may be
classified as follows: Figure 3: Piebaldism.

Diseases which are caused by abnormal migration of melanoblasts from the neuroectoderm
into the skin.
These include piebaldism (Figure 3) and the related Waardenburg syndrome. In
the more commonly occurring piebaldism, patients have a white forelock and there
is lacking pigmentation on the middle of the forehead, eyebrows and chin, and on
the central portion of the thorax, and abdomen. Around the margins of the

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Albinism is associated with a greater
than average risk of developing skin
cancer.
Phenylketonuria is diagnosed by the
Guthrie screening test on the 4th or
5th day of life.
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hypopigmented areas there are patches of hyperpigmentation. Piebaldism and
Waardenburg syndrome are sometimes also characterized by heterochromia of the
irises, hearing impairment, and Hirschsprung disease. Piebaldism is inherited in an
autosomal dominant pattern, and Waardenburg syndrome in an autosomal reces-
sive manner [8].
Diseases due to abnormal melanogenesis
Genetic defects in the melanin-forming enzyme tyrosinase can lead to a hereditary
pigmentation deficiency [4]. The resulting condition, known as albinism, has an in-
cidence of 1 : 5 000–1 : 40 000. Albinism refers to a mixed group of diseases which
may feature poor vision and nystagmus, as well as very light hair and skin. A distinc-
tion is made between oculocutaneous and purely ocular forms of albinism. In the oc-
ular form, there is discrete depigmentation of the skin and hair. Nine autosomal re-
cessive inheritance patterns and one autosomal dominant form as well as four other
types of ocular albinism have been identified to date. Albinism is associated with a
greater than average risk of developing skin cancer.
Menkes syndrome is a very rare X-chromosome disorder affecting copper metabo-
lism. The disease leads to psychomotor retardation, pili torti, pallor, seizures and
death in infancy or early childhood. There is marked skin pallor and laxity resembling
cutis laxa. The responsible gene has been identified as a copper-transporting ATPase.
Disruption of copper-dependent oxidation of tyrosine to dihydroxyphenylalanine
(DOPA) results in diminished tyrosinase activity which manifests clinically as diffuse
cutaneous hypopigmentation.
Phenylketonuria is a relatively common autosomal recessive metabolic disorder
which leads to a deficiency in phenylalanine hydroxylase. The lacking metabolic
pathway to tyrosine causes a relative deficiency in this normally non-essential amino
acid. Tyrosine is needed for synthesis of the neurotransmitter dopamine and of
thyroid hormones as well as for the production of the pigment melanin which is re-
sponsible for hair and skin color. The reported incidence of this disease is 1 : 6 000–1 :
16 000. Onset is during late infancy with motor retardation and later variously severe
mental retardation, microcephaly, and seizures. Patients are often fair-skinned with
blonde hair and blue eyes and often have a tendency to develop eczema. Occasionally
a typical smell may be present (phenylacetic acid). The disease is tested for during
neonatal screening, usually on the 4th or 5th day of life. Diagnosis is based on pheny-
lalanine concentrations in the blood (e.g., Guthrie test). Therapy consists of a diet
low in phenylalanine.
The group of disorders of abnormal melanogenesis includes the aminoacidopathies:
Histidinemia and homocystinuria are further diseases that involve pigmentation
disorders affecting the eyes, skin, and hair. Histidinemia results from deficient histi-
dase activity in the stratum corneum and liver. Similar to phenylketonuria there is an
alternative breakdown pathway via imidazole products, which may be detected in
urine. Diagnosis is based on detection of diminished enzyme activity in the stratum
corneum. Screening for the disorder is with a ferric chloride test (urine turns a green-
ish color). Patients with homocystinuria may have psychomotor retardation and var-
ious deformities as well as light skin and scalp hair that is fine, dry, sparse, and frag-
ile. Apparently, the high concentrations of homocysteine inhibit tyrosinase activity.
Rare syndromes are mentioned here as a reminder that if there is suspicion of genetic
causes underlying hypopigmentation, the physician should consult with a colleague
who has expertise in the respective area.
Diseases caused by abnormal melanosome formation
Examples of systemic diseases associated with abnormal biogenesis of melanosomes
include Hermansky-Pudlak (HPS) disease and Chediak-Higashi syndrome
(CHS). HPS is divided into eight different subtypes which are all caused by a genetic
disorder in the biogenesis of lysosomal organelles including melanosomes. Along
with tyrosinase-positive oculocutaneous albinism, patients with HPS have an in-
creased bleeding tendency due to lacking dense bodies in the thrombocytes [9]. The
disorder may be associated with restrictive lung disease and in rare cases can lead to
colitis or renal insufficiency. Abnormal melanosome formation leads to increased
sensitivity to UV light and a predisposition to actinic pre-cancerous lesions and skin
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Localized hypopigmentation
in early childhood

Complete absence Reduced

of pigmentation pigmentation

Mosiacism
Segmental Nevus Tuberous Post-infection Post-inflammatory
hypomelanosis of Ito,
vitiligo depigmentosus sclerosis
incontinentia pigmenti,
cutis tricolor

Figure 4: Algorithm for differential diagnosis of localized hypopigmentation at birth or during early
childhood. Based on Bolognia J (1999) A clinical approach to leukoderma. Int.J.Dermatol. 38:568–572.

neoplasias, as seen in patients with albinism. Diagnosis is based on clinical findings

and may be confirmed by molecular genetic testing.
CHS is defined by the presence of partial oculocutaneous albinism and an immune
deficiency syndrome. The cause is a mutation in the lysosomal trafficking regulator
(LYST) gene. This leads to dysregulation in the division and fusion of lysosomal or-
ganelles including melanosomes. The presence of giant melanosomes in the
melanocytes is a characteristic histological finding. The associated immune deficiency
manifests from the first month of life onward with pyogenic infections that originate
in the skin (impetigo, abscess, erysipelas) or from the respiratory system (sinus, phar-
ynx, lungs).

Diseases caused by abnormal melanosome transfer

Patients with Griscelli syndrome (GS) have diffuse hypopigmentation of the skin
and hair (GS1–3) associated with neurological (GS1) or immunological (GS2) disor-
ders. Abnormal transfer of melanosomes to the dendrites leads to an accumulation of
melanosomes in the melanocytes. Elejalde syndrome is also characterized by partial
albinism with characteristic silvery hair caused by abnormal melanosome transfer
from the melanocytes to the keratinocytes. Patients may also have severe neurological
deficits.

Hypomelanoses caused by various pathomechanisms

Patients with various forms of ectodermal dysplasias or storage diseases often have Diffuse and localized hypopigmenta-
pale skin and light hair. Molecular genetic testing may also be used for diagnosis, but tion at birth or during early childhood
should only be ordered to confirm a presumptive diagnosis after clinical inspection. may be a sign of complex systemic
disease.
Localized hypo- and depigmentation in early childhood (Figure 4)
In young children, localized hypopigmentation may appear following the lines of
Blaschko or along the dermatomes; alternatively, they may have a checker-board pat-
tern or bathing-suit appearance (Figure 1). Such patterns are usually indicative of ge-
netic mosaicism [10].
Hypomelanosis of Ito is a highly characteristic hypopigmentation that is present at
birth or appears during the first years of life. The affected areas are usually seen as uni-
lateral or bilateral striations or swirls. The disorder is considered a symptom rather
than a separate disease entity and is an expression of highly varied mosaicism. Associ-
ated developmental disorders involving the CNS, eyes, and bones can also occur.
Depigmented nevi are frequently divided somewhat arbitrarily by the size of their di-
ameter: type I nevus depigmentosus simplex is < 10 cm without any other findings
while, type II nevus depigmentosus simplex is > 10 cm also without associated find-
ings. If there are associated abnormalities, then one speaks of type I and type II
nevus depigmentosus complex respectively. Type I depigmented nevi are the most Type I depigmented nevi are the most
common localized depigmentation seen in healthy newborns, affecting 1 out of common localized depigmentation
130 newborns in the Caucasian population [6]. Histology shows a normal or reduced seen in healthy newborns, affecting
number of melanocytes which typically contain fewer melanosomes than usual. A 1 out of 130 newborns in the Caucasian
type I nevus depigmentosus simplex should be distinguished from a nevus anaemicus. population
The latter is also a congenital lesion, usually measuring 1 to 3 cm in size, which is

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Figure 5: Ash-leaf hypopigmentation in tuberous sclerosis.
The differential diagnosis of type II ne-
vus depigmentosus simplex includes
segmental vitiligo
The most important steps in diagnos-
ing tuberous sclerosis are clinical
examination with a Wood light to
identify ash-leaf spots of hypopig-
mentation which appear during the
first months of life and performing an
echocardiogram to detect a possible
rhabdomyoma.
Patients with vitiligo are more likely
than average to have other autoim-
mune disorders (Table 2).
Segmental vitiligo has a more favor-
able prognosis than the symmetrical,
diffuse variant.
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Table 2: Diseases commonly as-
sociated with vitiligo.
• Hypo-/hyperthyroidism
• Hashimoto’s thyroiditis
• Diabetes mellitus
• Addison disease
• Hypoparathyroidism
• Pernicious anemia, autoimmune
hemolytic anemia
• Chronic thrombocytopenia
• Dysgammaglobulinemia
• Lymphoproliferative disease
• Scleroderma
• Rheumatoid arthritis
• Myasthenia gravis
• Down syndrome
• Malignant melanoma
lighter than the surrounding area and with an irregular border. Given vasoconstric-
tion in the affected area, rubbing the skin does not produce reactive hyperemia. Ne-
vus anaemicus is more of a pharmacological than a histological change. Local hyper-
sensitivity of ␣-adrenergic receptors of the cutaneous blood vessels to catecholamine
has been shown. Type 2 nevus depigmentosus simplex develops during early child-
hood and presents with a checkerboard pattern or in a linear pattern. The differential
diagnosis of type II nevus depigmentosus simplex includes segmental vitiligo. While
type 2 nevus depigmentosus is a congenital lesion which does not change in size pro-
portional to the body, segmental vitiligo is an acquired disorder which demonstrates
a certain degree of variability over the course of disease. On histology, vitiligo lesions
lack melanocytes in the affected area.
In the autosomal dominant tuberous sclerosis, ash-leaf spots of hypopigmentation,
which are usually found on the trunk and proximal extremities, are present at birth or
develop during the first months of life (Figure 5). Along with angiofibromas on the
face, which appear during puberty, patients may have periungual and gingival fibro-
mas, connective tissue nevi on the lumbosacral region, and epileptic seizures. Imag-
ing studies show cerebral calcifications, renal hamartomas, and cardiac rhabdomy-
oma. More than three white spots, often only visible under a Wood light (UVA),
combined with epilepsy and mental retardation (not mandatory) should raise suspi-
cion of tuberous sclerosis. Two gene loci have been identified to date in tuberous scle-
rosis. Mutations in tuberin or hamartin are responsible for this phacomatosis. If clin-
ical suspicion is high, the presence of a rhabdomyoma on an echocardiogram is
associated with a high predictive value. The second most important test is a cranial
CT or MRI to detect cerebral calcifications. Differential diagnosis in a patient with
angiofibroma affecting the face and patch-like hypopigmentation should include
type I multiple endocrine neoplasia. This disorder is caused by protooncogene
MEN1 on chromosome 11q13.
Numerous dermatological diseases can lead to localized depigmentation (Figures 4
and 6) [11]. Vitiligo is especially common, with an incidence of around 1 : 200 [12].
Vitiligo may manifest in childhood or it may not appear until adulthood. Disease
may be segmental or diffuse. Vitiligo is an autoimmune disorder that causes destruc-
tion of melanocytes. Patients with vitiligo are more likely than average to have other
autoimmune disorders (Table 2). Vitiligo generally begins on the hands and feet and
then spreads to the extensor aspects of the joints and to the face (Figure 7). Segmen-
tal vitiligo has a more favorable prognosis than the symmetrical, diffuse variant.
Localized post-inflammatory hypopigmentation is common and may occur after
various inflammatory skin disorders. Another frequent type of acquired hypopigmen-
tation in children is pityriasis alba, which is more common in patients with atopic
dermatitis. The etiology of pityriasis alba has not yet been fully explained. Histology
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Hypopigmentation in adulthood

Generalized Localized

Whole-body Pan-hypo- Post- Post-inflammatory Post-infectious Diverse

vitiligo pituitarism traumatic disorders
-Atopic dermatitis -Syphilis
-Pityriasis alba -Pityriasis rosea
-Psoriasis -Tuberculoid leprosy
-Lichen striatus
-Lichen sclerosus et atrophicus
-Pityriasis lichenoides chronica
-Hypomelanosis guttata
-Progressive macular hypomelanosis

Chemical Melanoma-induced
Vitiligo Scleroderma
leukoderma leukoderma

Vogt-Koyanagi-Harada
disease

Figure 6: Algorithm for differential diagnosis of diffuse hypopigmentation in adulthood. Based on

Bolognia J (1999) A clinical approach to leukoderma. Int.J.Dermatol. 38:568–572.

Figure 7: Vitiligo.

usually shows unspecific chronic dermatitis. In addition there is diminished pigmen-

tation in the basal cell layer of the epidermis. Under electron microscopy the number
and size of melanosomes may be reduced.

Hypopigmentation in adults (Figure 6)

Diffuse hypopigmentation can occur in conjunction with disorders of the anterior Hormonal imbalances are a common
hypophysis (pan-hypopituitarism, Simmonds disease). Patients may have wax-colored cause of disorders of pigmentation.
or almost alabaster skin as a result of lacking melanocyte-stimulating hormones. Causes
include hypophyseal tumors, postpartum ischemia (Sheehan syndrome), granulomato-
sis, and inflammatory disorders. Deficient levels of hypophyseal effector hormones
(somatotropin, prolactin) and glandotropic hormones (ACTH, TSH, LH, FSH) with
secondary insufficiency of the peripheral glands are characteristic. The symptoms are
the result of multiple hormonal deficits and include weakness, adynamia, hypotension,
secondary amenorrhea, impotence, loss of libido, loss of secondary body hair and the
hair of the lateral portions of the eyebrows, sensitivity to cold, and a tendency to hypo-
glycemia. A clinical presumptive diagnosis is confirmed by a lacking increase in serum
hypophyseal hormones after stimulation by synthetic hypothalamic releasing hormone

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Figure 8: Hypomelanosis guttata idiopathica.

(combined CRH/TRH/GnRHtest). Ophthalmological, neurological, and radiological

tests can also provide important evidence, e.g., for hypophyseal tumors (bitemporal
hemianopsia, signs of intracranial pressure, pituitary saddle defects).
The presence of congenital or acquired hypopigmentation can assist in the diagnosis
of various systemic diseases [13]. One disorder associated with acquired hypopigmen-
tation in adulthood (vitiligo) is Vogt-Koyanagi-Harada syndrome. Symptoms in-
clude inflammation of the uvea, retinal pigment layer, and meninges. An association
with encephalitis or cranial nerve dysfunction is not uncommon.
Melanoma can lead to a confetti-like depigmentation resembling vitiligo, especially
when metastatic. Depigmentation with malignant melanoma has also been observed
after various therapies including radiation therapy, cytokine therapy, BCG and other
vaccinations. Cytotoxic antibodies and activated lymphocytes seem to exhibit cross-
reactivity with melanoma cells and benign melanocytes.
The appearance of an acquired, ring-like depigmentation around an existing
melanocytic nevus is referred to as a halo or Sutton nevus. Depigmentation can
progress to complete regression of the nevus. Halo nevi usually affect adolescents and
young adults. Characteristic histological findings include a compound nevus, a dense
lymphocytic infiltrate in the nevus parenchyma, and loss of melanocytes and melanin
in the halo, which is suggestive of an immunological reaction.
Localized hypo- and depigmentation can result from direct chemical or pharmaco-
logical effects. The most important substances are monobenzyl ether, hydroquinone,
and benzoyl peroxide.
Inflammatory skin diseases such as psoriasis or atopic dermatitis or lichen sclerosus et
atrophicus may be associated with localized post-inflammatory depigmentation [14].
Idiopathic hypomelanosis guttata with confetti-like depigmentation is a very com-
mon disorder affecting the lower legs and the arms in patients with actinic skin dam-
age at these sites (Figure 8).
Progressive macular hypomelanosis (PMH) can usually be diagnosed by its differ-
ent pattern of involvement. PMH is characterized by hypopigmented, nummular,
non-scaling macules on the trunk which frequently merge along the midline and
rarely affect the proximal extremities or head-and-neck region (Figure 9). PMH has
become more common in recent years and is now seen also in Europe, especially
among dark-skinned patients who have emigrated from tropical countries, more
prevalent in young females. Climate change seems to be playing a role in this trend.
Propionibacterium acnes also plays a major part in the pathogenesis of the disease [15],
in that a factor produced by P. acnes interferes with melanogenesis, leading to reduced
melanin production and an altered melanosome distribution. In lesional skin, groups
of less highly melanized melanosomes – in place of individual, mature melanosomes
– are transferred from the melanocytes to the keratinocytes.

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Table 3: Congenital diffuse hy-

perpigmentation.
• Endocrine disorders
• Porphyria, hemochromatosis
• Nephropathies, hepatopathies
• Malnutrition
• Lymphogranulomatosis
• Metastasizing melanoma
• Medication

Figure 9: Progressive macular hypomelanosis.

The localized, macular or the mixed biphasic (macular and lichenoid variant) of amy-
loidosis may be associated with de- or hyperpigmentation hence the term vitiliginous
amyloidosis. Affected patients often have pruritus leading to scratching which in
turns exacerbates the pigmentation disorder.
Leukoderma is an expression of cutaneous sarcoidosis with an incidence of 6 %.
Lesions are poorly-bordered papular or plaque-like changes measuring a few centime-
ters in diameter. The lesions seen in discoid lupus erythematosus may appear nearly
identical. Scleroderma may present with patch-like hyperpigmentation as well as
with vitiligo-like depigmentation which then is often related to pulmonary-arterial
hypertension [16]. Hypopigmented mycosis fungoides, a form of cutaneous T-cell
lymphoma, is more common in children. Post-infectious pigmentation lightening
is sometimes relevant for diagnosis as in secondary syphilis or tuberculoid leprosy.
Both onchocercosis and post-kala-azar dermatitis may be associated with patchy de-
pigmentation. Malnutrition leads to a typical “flag sign” as in kwashiorkor with
band-like hypopigmentation of the hair which occur periodically and represent peri-
ods of severe malnutrition. The skin also becomes lighter [14].

Hyperpigmentation
Darkening of the skin pigmentation may be an expression of banal skin adaptation
(tanning) or it may be a sign of life-threatening disease (e.g., metastasizing
melanoma) [17, 18].

Congenital diffuse hyperpigmentation

Melanosis diffusa congenita, alternatively known as familial progressive hyperpig-
mentation, universal acquired melanosis, or carbon baby, is a congenital diffuse dirty
brown hyperpigmentation covering the skin. The disease is presumably inherited in
an autosomal dominant pattern. No other organs are affected. There is a tendency for
the skin to become somewhat lighter during adulthood. Histology reveals increased
melanin throughout the epidermis and into the stratum corneum. The etiology of the
disorder is unknown.

Acquired diffuse hyperpigmentation

A diffuse brown skin coloration may be caused by various endocrine disorders and is
especially typical for primary adrenal cortical insufficiency (Addison disease) (Table 3).
Addison disease is caused in more than 50 % of patients by an autoimmune disor-
der. In 25–30 % of patients autoantibodies to adrenal cortex tissue are detected.
Often additional antibodies to the thyroid, gonads, gastric mucosa, and intrinsic
factor are found. Tuberculosis, hemorrhage, or metastasizing carcinoma can also

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196 Academy
Figure 10: Addison disease with increased pigmentation especially along the lines of the hand.
An early symptom of Addison disease
is brown discoloration of the skin
which is more intense on sun-
exposed areas and at pressure sites,
scars, nipples, genitals, along lines of
the hands and on the mucosae. Diag-
nosis is confirmed by a short ACTH
stimulation test.
JDDG | 3 ˙2010 (Band 8)
Figure 11: Laugier-Hunziker syndrome.
cause Addison disease. Patients with adrenoleukodystrophy also develop Addison dis-
ease. Typical symptoms in Addison disease are signs of corticosteroid deficiency such
as adynamia, hypothermia, fatigue, hypotension, weight loss, dehydration, diarrhea,
vomiting, and a tendency to hypoglycemia. In severe cortisone deficiency, muscle
cramps as well as paresis can occur due to hyperkalemia. Additional symptoms are
loss of secondary body hair in women and psychosexual disorders with menstrual cy-
cle anomalies and loss of libido. In patients with a glucocorticosteroid deficiency, the
negative feedback mechanism on the hypothalamic-pituitary axis is absent leading to
increased production of ACTH and its precursor proopiomelanocortin. Proopiome-
lanocortin is also the precursor for ␤-lipotropin and ␥-melanotropin (␥-MSH), ␤-
MSH and ␣-MSH, whose melanocyte-stimulating effect is responsible for the brown
color of the skin. Hyperpigmentation usually precedes other symptoms of disease and
is intensified at sites that are exposed to light and pressure, in the skin folds, lines of
the hands, nipples and areas of scarring (Figure 10). Lentiginous pigmentation may
be found on the oral mucosa, lips, and anogenital regions.
This form of mucosal pigmentation should be distinguished from Peutz-Jeghers
syndrome (PJS). The autosomal-dominant PJS leads to polyposis with an overall
increase in carcinoma incidence in the intestinal mucosa, pancreas, lungs,
breasts, ovaries, and endometrium (evidence level B). The disorder is caused by a
mutation in the serine/threonine-kinase gene STK11. Laugier-Hunziker
syndrome presents with pigmentary changes similar to Peutz-Jeghers syndrome,
but without intestinal polyps; familial incidence has also not been adequately con-
firmed (Figure 11 a, b).
In Addison disease about 10 % of patients have vitiligo as an expression of a possi-
ble autoimmune genesis. Eosinophilia sometimes develops as well, and its presence
can aid diagnosis especially in patients with an Addisonian crisis and disordered con-
sciousness because other comatose conditions are rarely associated with eosinophilia.
Routine laboratory parameters (electrolytes, blood sugar, blood count) are helpful,
but presumptive diagnosis is based on clinical signs and confirmed by an ACTH
stimulation test. Diagnosis can also be confirmed by determining ACTH concentra-
tions in plasma, which are significantly raised in Addison disease (up to 1500 pg/ml;
normal range 20–100 pg/ml). Secondary adrenal insufficiency is not uncommon in
patients with widespread chronic inflammatory skin disease who have been using
topical steroids for a longer period of time.
Acromegaly and Cushing syndrome can lead to diffuse hyperpigmentation, which
is presumably caused by stimulation of melanocyte activity by MSH. A corticotropic
adenoma of the hypophysis (Nelson tumor) can cause excessive secretion of ACTH
and darkening of the skin.
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About 2 % of patients with hyperthyroidism develop diffuse hyperpigmentation

which usually does not affect the oral mucosa. Histology shows increased melanosis
of the basal layer and greater deposition of hemosiderin in the dermis, the latter of
which results from increased capillary fragility due to thyrotoxicosis.
During pregnancy, hyperpigmentation can occur on the face (melasma or chloasma),
nipples, linea alba, and anogenital regions. Both estrogens and gestagens appear to
play a role, as does perhaps ␤-lipoprotein, which is synthesized by the pituitary gland
and has a melanotropic effect.
Diffuse but less severe hyperpigmentation may occur in patients with cancer or
chronic diseases such as tuberculosis. Case control studies have reported diffuse
melanosis of uncertain pathogenesis in up to 47 % of patients with primary biliary
cirrhosis in which unceasing pruritus is a chief clinical symptom, occurring long be-
fore icterus. UV-exposed areas of the skin were reportedly affected more strongly. The
disease is much more common in women than men. An important diagnostic labo-
ratory parameter is the presence antimitochondrial antibodies.
Hemochromatosis is also referred to as bronze diabetes, because along with abnor-
mal metabolic function over time patients develop a grayish or brown skin tone. Hy-
perpigmentation occurs in 70 %, mainly affecting the face and hands and sometimes
with mucosal changes. Hyperpigmentation of the skin is, on the one hand, caused by
increased melanogenesis with increased melanin in the epidermis and in dermal
melanophages, and on the other by iron deposits in the deeper dermis. Excess iron re-
sults in functional disorders affecting various organs (liver, pancreas, heart, gonads).
Diagnostic signs include high ferritin levels. Along with a liver biopsy, molecular ge-
netic mutation testing can be used to confirm presumptive diagnosis. Other forms of
chronic liver disorders also demonstrate a marked brown discoloration of the skin,
usually combined with pruritus.
Hepatolenticular degeneration (Wilson disease) is caused by a genetic disorder
of copper metabolism leading to neurological symptoms with a typical tremor
caused by copper deposits in the basal ganglia. Patients also have progressive
cirrhosis of the liver. A pathognomic sign is a green-brown Kayser-Fleischer ring
around the cornea, which is often only detectable with a slit lamp. Diffuse
hyperpigmentation is seen on the skin of such patients, especially on the lower
extremities and there may be a greenish tone to the facial skin and bluish lunulae
on the nails.
Forms of porphyria with cutaneous involvement include porphyria cutanea tarda
(PCT), congenital erythropoietic porphyria (Gunther disease; CEP), erythropoietic
protoporphyria (EPP), hereditary coproporphyria (HC), and porphyria variegata
(PV). All cutaneous forms of porphyria with the exception of EPP present with frag-
ile skin and blistering on UV-light exposed areas of the skin. The cutaneous clinical The cutaneous clinical manifestations
manifestations of PCT, CEP, HC and PV can be so similar that biochemical testing is of PCT, CEP, HC and PV can be so simi-
needed for accurate diagnosis. These are also grouped under the term “bullous por- lar that biochemical testing is needed
phyrias.” PCT, CEP, HC and PV often show hypertrichosis, especially around the for accurate diagnosis. These are also
temples as well as increased pigmentation particularly on sun-exposed areas of the grouped under the term “bullous por-
skin. Porphyrins cause a phototoxic reaction with development of erythema, edema, phyrias.”
blisters, erosions, and ulcerations. Healing may result in scarring, hyperkeratosis, hy-
pertrichosis or areas of depigmentation. A characteristic feature reported by patients
is discoloration of urine, ranging from red-brown to deep red. Clinical diagnosis is
confirmed by analysis of porphyrin metabolites depending on the form of porphyria
in urine, blood, or stool.
Chronic renal insufficiency is characterized by a dirty gray-yellow-brown skin color.
The skin color results from the combination of anemia and pigment deposits
(melanin, urochrome).
Brown pigmentation of the skin is typical in advanced systemic sclerosis (SSc), even
without renal involvement. The precise mechanism of diffuse hyperpigmentation in
SSc is unknown. Recent studies have suggested that endothelin-1 may play a role in
pathogenesis. Endothelin-1 is not only present in greater amounts in endothelial cells
in patients with SSc, it is also produced by epidermal keratinocytes. There is a posi-
tive correlation between endothelin-1 production of keratinocytes and the degree of
hyperpigmentation in SSc. It is presumed that endothelin-1 stimulates epidermal
melanogenesis.

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198 Academy
Causes of acquired diffuse hyperpig-
mentation include hormonal imbal-
ance, renal insufficiency, liver disease,
and drug-related side effects.
2 % of the Caucasian population has a
café-au-lait spot at birth.
More than 5 café-au-lait lesions are
suggestive of neurofibromatosis. A
search should be made for axillary
freckling (Crowe sign) and iris hamar-
tomas (Lisch nodules).
Rarer genetic syndromes such as
Albright syndrome and Cowden
syndrome are also associated with
café-au-lait spots.
JDDG | 3 ˙2010 (Band 8)
Figure 12: Unilateral lentiginosis.
Patients with Felty syndrome may have chronic polyarthritis, neutropenia, or
splenomegaly. About 20 % of patients with Felty syndrome also have hyperpigmentation,
which on the one hand is due to increased epidermal melanin, and on the other to
dermal hemosiderin deposition. Hemosiderin deposits due to vasculitis and skin
hemorrhage lead to iron-induced stimulation of melanocytes. Hyperpigmentation
may be exacerbated by various therapies: Dermal gold deposits stimulate melanin
production and lead to photoaccentuated hyperpigmentation, and further antimalar-
ial drugs (quinacrine, chloroquine, and hydroxychloroquine) can lead to hyperpig-
mentation of the skin and mucous membranes.
In addition to the anti-malarial agents, other medications, such as amiodarone,
minocycline, antiretroviral drugs, and chemotherapy drugs can lead to localized and
diffuse hyperpigmentation [19].
Localized hyperpigmentation of genetic origin
There are a vast number of genodermatoses which involve hyperpigmentation. Ecto-
dermal dysplasias in particular encompass various entities with reticular pigmentation
on the neck such as Naegeli-Franceschetti-Jadassohn syndrome and dyskeratosis con-
genita [20]. Linear, quadrant-like, and mid-line hyperpigmentation can occur in ge-
netic mosaicism (Figure 1).
Localized hyperpigmentation at birth or in childhood
Café-au-lait spots may be present at birth or develop during the first years of life.
2 % of the Caucasian population has a café-au-lait spot at birth. Café-au-lait spots
have a uniform pigmentation and a sharp border. They range in size from 0.2 cm to
30 cm in diameter. The brown color is caused by an increase in melanin content of
the melanocytes and basal keratinocytes. Café-au-lait spots are also markers for vari-
ous genodermatosis, especially neurofibromatosis [21]. More than 5 café-au-lait le-
sions are suggestive of neurofibromatosis. A search should be made for axillary freck-
ling (Crowe sign) and iris hamartomas (Lisch nodules). The diagnostic guidelines of
the National Institutes of Health (NIH) correspond to evidence level C (consensus
recommendation). Rarer genetic syndromes such as Albright syndrome and Cow-
den syndrome are also associated with café-au-lait spots.
Lentigines are dark 2–20 mm large macules which can occur anywhere on the skin
(Figure 12). Lentigo simplex is characterized by thin elongated rete ridges, epider-
mal hyperpigmentation, and increased amounts of melanin. The number of
melanocytes increases proportionally to the elongation of the rete ridges. The
melanocytes are arranged in single-file in the basal cell layer. In ephelides, there is
also an increase in melanin in the basal epidermis, but no elongation of the
rete ridges. The same is true for lentigines of the mucous membranes. Various
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Figure 13: Becker nevus syndrome.

syndromes are associated with lentigines, ephelides and melanotic mucosal spots.
LEOPARD syndrome is an acronym for Lentiginosis, electrocardiographic
changes, ocular hypertelorism, Pulmonary stenosis, abnormalities of the genitalia,
retarded growth, and deafness. The multiple lentigines in LEOPARD syndrome are
lentigines simplices. Café-au-lait spots and melanocytic nevi may also be present.
The responsible gene codes for the synthesis of protein-tyrosine-phosphatase non-
receptor type 11 (PTPN 11). Carney complex is also known by the acronyms
LAMB syndrome (Lentigines, atrial myxomas, mucocutaneous myxomas, and blue
nevi) or NAME syndrome (Nevi, atrial myxomas, myxoid neurofibromas, and
ephelides). Localized hyperpigmentation may include lentigines, ephelides, melan-
otic patches on the lips, and blue nevi. There is a defect for a tumor suppressor gene
that codes for the regulatory subunit 1-␣ of the cAMP-dependent protein kinase A
(PRKAR 1a).
Hypermelanosis naeviformis (Becker nevus) presents with a unilateral hamartoma,
an organoid nevus, which exhibits hyperpigmentation and has a border resembling an
archipelago. The lesion commonly affects the shoulder region. During puberty there
is brown discoloration and growth of dark and thicker hair on the lesion. Histology
shows increased amounts of melanin in the basal cell layer with a normal number of
melanocytes. There is also epidermal acanthosis and hyperplasia of dermal smooth
muscle fibers. Nests of nevus cells as seen in melanocytic nevi are absent. There is no
particular risk of malignant transformation. The rare Becker nevus syndrome fea-
tures ipsilateral hypoplasia of the breast tissue and pectoral muscle, often combined
with scoliosis and urogenital malformations (Figure 13).

Acquired localized hyperpigmentation

Melasma is a localized hyperpigmentation of the face that occurs in women especially
in conjunction with hormonal changes. Melasma is divided into epidermal and der-
mal types. In the epidermal form, there is increased deposition of melanin in basal
and suprabasal epidermal layers. In the dermal type melanin is deposited in increased
amounts in perivascular macrophages of the upper and deep vascular plexus. In both
types the melanocytes produce increased amounts of melanin. There is an increased
number of melanosomes in the dendrites of the melanocytes. 87 % of women who 87 % of women who have melasma
have melasma under oral contraceptive use are also affected during pregnancy. There under oral contraceptive use are also
appears to be a certain predisposition for hormonal stimulation of melanocytes. affected during pregnancy.
Melasma has also been reported after taking phenytoin and in HIV.
Diabetic dermopathy is found in up to 70 % of patients with diabetes. A typical sign
is maculopapular brownish discoloration on the shins.
Pityriasis versicolor (flavus type), which is caused by Malassezia furfur, can lead to
brownish or reddish skin discoloration. This hyperpigmented form is not caused by

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200 Academy

melanin. Histology shows a thickened stratum corneum. Malassezia furfur is also able
to block transformation of tyrosine in melanin, which can lead to the hypopigmented
variant of pityriasis versicolor (albus type). A specimen of this superficial fungus can
be collected with Scotch tape and stained with methylene blue, which reveals typical
“spaghetti-and-meatball” appearance.
Hypopigmentation or - often transitory - hyperpigmentation can also result from physi-
cal or chemical trauma, chronic irritation, or inflammatory skin disease [22]. <<<

Conflict of interest
None.

Correspondence to
Prof. Dr. med. Peter Itin
Dermatologie
Universitätsspital
Petersgraben 4
CH-4031 Basel, Schweiz
Tel.: +41-61-265-4084
Fax: +41-61-265-4885
E-mail: pitin@uhbs.ch

References
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2 Nordlund JJ, Boissy RE, Hearing VJ, King R, Oetting W, Ortonne JP. The Pigmentary
System, 2nd Edition, Wiley-Blackwell, 2006.
3 Holland ND. Early central nervous system evolution: an era of skin brains? Nat Rev
Neurosci 2003; 4: 617–27.
4 Rees JL. The genetics of sun sensitivity in humans. Am J Hum Genet 2004; 75:
739–51.
5 Seghal VN, Srivastva G. Hereditary hypo/de-pigmented dermatoses: an overview. Int J
Dermatol 2008; 47: 1041–50.
6 Ruiz-Maldonado R. Hypomelanotic conditions of the newborn and infant. Dermatol
Clin 2007; 25: 373–82.
7 Bolognia J. A clinical approach to leukoderma. Int J Dermatol 1999; 38: 568–72.
8 Spritz RA, Itin PH, Gutmann DH. Piebaldism and neurofibromatosis type 1: horses of
very different colors. J Invest Dermatol 2004; 122: 34–5.
9 Herskovitz D, Sprecher E. Monogenic pigmentary skin disorders: genetics and patho-
physiology. Isr Med Assoc J 2008; 10: 713–7.
10 Itin P, Burger B. Mosaic manifestations of monogenic skin diseases. J Dtsch Dermatol
Ges 2009; 7: 744–9.
11 Orlow SJ. Congenital and genetic disorders associated with hypopigmentation. Curr
Probl Derm 1994; 161–84.
12 Taieb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med 2009; 360: 160–9.
13 Mollet I, Ongenae K, Naeyaert JM. Origin, clinical presentation, and diagnosis of hy-
pomelanotic skin disorders. Dermatol Clin 2007; 25: 363–71.
14 Ruiz-Maldonado R, Orozco-Covarrubias ML. Postinflammatory hypopigmentation
and hyperpigmentation. Sem Cutan Med Surg 1997; 16: 36–43.
15 Relyveld GN, Menke HE, Westerhof W. Progressive macular hypomelanosis: an
overview. Am J Clin Dermatol 2007; 8: 13–9.
16 Coral-Alvarado P, Rojas-Villarraga A, Latorre MC, Mantilla RD, Restrepo JF, Pardo
AL, Chalem P, Rondón F, Jáuregui E, Rueda JC, Cañas C, Hincapie ME, Pineda-
Tamayo R, Alvarez F, Iglesia-Gamarra A, Diaz FJ, Anaja JM. Risk factors associated
with pulmonal arterial hypertension in colombian patients with systemic sclerosis: re-
view of the literature. J Rheumatol 2008; 35: 244–50.
17 Fulk ChS. Primary disorders of hyperpigmentation. J Am Acad Dermatol 1984; 10:
1–16.
18 Stefanato CM, Bhawan J. Diffuse hyperpigmentation of the skin: a clinicopathologic
approach to diagnosis. Sem Cutan Med Surg 1997; 16: 61–3.

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19 Hendrix JDJr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int
J Dermatol 1992; 31: 458–66.
20 Itin PH, Lautenschlager S. Genodermatosis with reticulate, patchy and mottled pig-
mentation of the neck – a clue to rare dermatologic disorders. Dermatology 1998; 197:
281–90.
21 Landau M, Krafchik BR. The diagnostic value of café-au-lait macules. J Am Acad Der-
matol 1999; 40: 877–90.
22 Lacz NL, Vafaie J, Kihiczak NI, Schwartz RA. Postinflammatory hyperpigmentation: a
common but troubling condition. Int J Dermatol 2004; 43: 362–5.

Fragen zur Zertifizierung durch die DDA

1. Welche Antwort ist richtig? d) Das Verhältnis der Melanozyten d) Das Waardenburg-Syndrom wird
a) Die Hautfarbe wird vorwiegend zu Baselzellen beträgt 1:4 bis 1:9. durch einen gestörten Melanoso-
durch den Hämoglobingehalt e) a–d sind falsch. mentransfer bedingt.
bedingt. e) Keine der Antworten ist richtig.
b) Die Hautfarbe wird vorwiegend 4. Welche Antwort ist nicht richtig?
durch die Zahl der Melanozyten a) Hypopigmentierungen können 6. Welche Aminoazidurie führt als
bedingt. durch fehlende Migration der Zusatzproblem zu brüchigen Haaren?
c) Die Hautfarbe wird vorwiegend Melanoblasten von der a) Phenylketonurie
durch den Karotingehalt bedingt. Neuralleiste in die Haut b) Alkaptonurie
d) Die Hautfarbe wird vorwiegend entstehen. c) Homozystinurie
durch die Zahl der Melanosomen b) Hyperpigmentierungen können d) Cystinose
bedingt. durch gestörten Transfer von e) Oxalose
e) Die Hautfarbe wird vorwiegend Melanosomen in die umliegenden
durch exogene Pigmente bedingt. Keratinozyten entstehen. 7. Die Häufigkeit der Vitiligo in der
c) Hypopigmentierungen können Weltbevölkerung wird angegeben
2. Welche Antwort ist richtig? durch einen Tyrosinsynthese- mit:
a) Dunkle Rassen weisen vorwiegend Defekt entstehen. a) 0,01 %
Eumelanin auf. d) Hyperpigmentierungen können b) 0,5 %
b) Dunkle Rassen weisen vorwiegend durch gestörten Melanosomenab- c) 1 %
Phäomelanin auf. bau entstehen. d) 5 %
c) Dunkle Rassen weisen einen De- e) Hypo- und Hyperpigmentierun- e) 10 %
fekt im Tyrosinmetabolismus auf. gen können postinflammatorisch
d) Dunkle Rassen haben mehr entstehen. 8. Welche Antwort ist richtig?
Melanozyten als helle Rassen. a) Beim Panhypopituitarismus
e) Dunkle Rassen steuern ihr 5. Welche Antwort ist richtig? entsteht eine diffuse
Pigment mit dem Hormon a) Das Waardenburg-Syndrom wird Hyperpigmentierung der Haut.
Melatonin. verursacht durch eine gestörte Mi- b) Beim Panhypopituitarismus
gration der Melanoblasten aus entsteht eine diffuse
3. Welche Aussage ist falsch? dem Neuroektoderm. Hypopigmentierung der Haut.
a) Ein Melanozyt versorgt etwa 36 b) Das Waardenburg-Syndrom ist c) Beim Panhypopituitarismus
keratinozyten mit Melanosomen. eine Krankheit durch eine gestörte entsteht eine phylloide Hypopig-
b) Eumelanin entspricht dem braun- Melaninsynthese. mentierung.
schwarzen Farbton. c) Das Waardenburg-Syndrom ist d) Beim Panhypopituitarismus
c) Phäomelanin entspricht dem rot- gekennzeichnet durch eine entsteht eine blaschko-lineäre
gelblichen Farbton. gestörte Melanosomenformation. Hyperpigmentierung.

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202 Academy

e) Beim Panhypopituitarismus en- d) Die progressive makulöse c) Die Verdachtsdiagnose eines

twickeln sich zunehmend Lentigines.
9. Welche Antwort ist richtig?
a) Die progressive makulöse
Hypomelanose wird durch eine
Autoimmunerkrankung bedingt,
welche zur Zerstörung der
Melanozyten führt.
b) Die progressive makulöse Hypome-
lanose wird durch Corynebacterium
diphtheriae verursacht.
c) Die progressive makulöse
Hypomelanose ist Ausdruck
einer Malnutrition.
Hypomelanose wird durch
Propionibacterium acnes bedingt.
e) Die progressive makulöse
Hypomelanose ist eine Spielform
der Syphilis.
10. Welche Antwort ist richtig?
a) Die Verdachtsdiagnose eines
Morbus Addison wird gesichert
durch eine Biopsie.
b) Die Verdachtsdiagnose eines
Morbus Addison wird gesichert
durch eine
Hypophysenaufnahme.
Morbus Addison wird gesichert
durch Nachweis von
Antikörpern gegen
Nebennierenrindengewebe.
d) Die Verdachtsdiagnose eines
Morbus Addison wird gesichert
durch einen ACTH-Stimulation-
stest.
e) Die Verdachtsdiagnose eines
Morbus Addison wird gesichert
durch die Pigmentierung der
Linea alba.

Liebe Leserinnen und Leser,

der Einsendeschluss an die DDA für diese Ausgabe ist der 16. April 2010.
Die richtige Lösung zum Thema ,,Hereditäre Palmoplantarhyperkeratasen“ in Heft 11 (November 2009) ist:
1d, 2c, 3e, 4a, 5b, 6b, 7d, 8b, 9d, 10a.
Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung online
unter http://jddg.akademie-dda.de ein.

JDDG | 3 ˙2010 (Band 8) © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0803