13 - 77 - HYPERMELANOSES Flashcards
- congenital condition causing** diffuse streaky hyperpigmented macules along the lines of Blaschko** without preceding inflammation or atrophy in the first few weeks of life
- Lesions are typically located on the trunk and limbs and do not cross the midline.
- Face, palms, soles, eyes, and mucous membranes are spared.
Linear and whorled nevoid hypermelanosis
X-linked dominant disorder resulting from mutation in the IKBKG (previously called NEMO) gene.
INCONTINENTIA PIGMENTI
- Congenital diffuse reticular hyperpigmentation with nail atrophy and leukoplakia.
- Manifests in the first few years of life.
- Extracutaneous manifestations are bone marrow failure and malignancies.
DYSKERATOSIS CONGENITA
- **Reticulate hyperpigmentation **is most prominent in **neck and axillae. **
* Palmoplantar diffuse keratoderma, **absence of dermatoglyphs, nail and teeth changes, **and heat intolerance owing to diminished or absent sweating are characteristic.
NAEGELI-FRANCESCHETTI- JADASSOHN SYNDROME
Naegeli-Franceschetti-Jadassohn syndrome and the related dermatopathia pigmentosa reticularis are autosomal dominant ectodermal dysplasias caused by mutations in what keratin?
KRT14 gene
* Reticulate hyperpigmentation on the trunk,
* **palmoplantar keratoderma **with punctiform accentuation,
* **nail and ocular **changes,
* noncicatricial alopecia,
* ichthyosis,
* hypohidrosis,
* widespread hyperkeratotic lesions,
* ainhum formation,
* severe periodontal disease,
* mechanic blister formation, and
* pigmentation of the oral mucosa
DERMATOPATHIA PIGMENTOSA RETICULARIS
- Autosomal dominant
- Numerous small symmetrical brown-gray macules usually begin in the groin and axillae in the third or fourth decade of life and then spread to intergluteal and inframammary folds, neck, trunk, and arms.
- Comedo-like hyperkeratotic follicular papules on the neck and axilla and pitted perioral acneiform scars also appear.
DOWLING-DEGOS DISEASE
mutation in DOWLING-DEGOS DISEASE
KRT5 gene
- show the diagnostic features of Dowling-Degos disease with the additional histopathologic finding of acantholysis in suprabasal epidermal layers
- It is regarded as the **acantholytic variant of Dowling-Degos disease. **
- Mutations in the keratin 5 gene have been found in some patients.
Galli-Galli disease
* angular and sharply demarcated reticulate, freckle-like hyperpigmented macules beginning on the dorsa of the hands during the first decade of life and subsequently spreading to the rest of the body
* The **macules are slightly depressed; **sometimes palmar pits can be observed.
* Most cases are from Japan.
Kitamura reticular acropigmentation
Mutations in the ADAM10 gene
- reticulate pigmentation on trunk and axillae
- verruciformis papular lesions of the trunk and a distinct photosensitive rosacea-like facial erythema and telangiectasias, most commonly presenting in childhood
HABER SYNDROME
Nevus of ota presents with unilateral blue-black or gray-brown dermal melanocytic pigmentation that is typically seen in areas innervated by what cranial nerve?
first and second branches of the trigeminal nerve
Of those affected with nevus of ota, how many % have scleral pigmentation?
60%
Other sites of mucosal pigmentation include the conjunctiva and tympanic membrane (oculodermal melanocytosis)
subclassifications of nevus of Ota
mild (Type 1),
moderate (Type 2),
intensive (Type 3),
bilateral (Type 4)
Malignancy that rarely develop in a nevus of Ota
Malignant melanoma
- this necessitates careful followup of the lesion, especially if it occurs in white patients, in whom malignant degeneration seems to be more frequent.
- Malignant melanocytic tumors in association with nevus of Ota have been shown to arise in the chorioidea, brain, orbit, iris, ciliary body, and optic nerve.
- association with **ipsilateral glaucoma **and intracranial melanocytosis has been described.
Various triggers that have been described in nevus of ota.
infection, trauma, ultraviolet light exposure, and hormonal influences,
Well-circumscribed, blue-tinged hyperpigmented macules in the sacral area are most commonly seen
Mongolian spots
- also can be found in the gluteal and lumbar regions and on the thorax, abdomen, arms, legs, and shoulders
Several cases are described with extensive Mongolian spots involving large areas of the trunk and extremities that are associated with what condition?
inborn errors of metabolism, such as lysosomal storage diseases, GM1-gangliosidosis and mucopolysaccharidosis
Histologically, these macules consist of **spindle-shaped melanocytes **in the lower dermis that have failed to migrate to the dermal–epidermal junction during fetal life.
Mongolian spots
nerve distribution of nevus of Ito
Acromioclavicular nerve
More than half of all cases of Peutz-Jeghers Syndrome can be attributed to a mutation in what?
STK11 (LKB1)
hallmarks of Peutz-Jeghers Syndrome
Mucocutaneous pigmentation and intestinal hamartomatous polyposis
most common malignancies associated with PJS
GI (small intestine, colorectal, stomach, pancreas)
but nongastrointestinal neoplasms, such as breast, cervix, and endocrine tumors (thyroid, testicular, ovarian), have been described.
LEOPARD syndrome is a rare autosomal dominant condition caused by a heterozygous missense mutation in what gene?
PTPN11 gene
spotty skin pigmentation, myxomas (heart, skin, breast), endocrine tumors (primary pigmented nodular adrenal disease [Cushing syndrome], testicular large-cell calcifying Sertoli cell tumor [sexual precocity], pituitary adenoma [acromegaly], thyroid tumors, ovarian cysts), and schwannomas
CARNEY COMPLEX
The typical lesions consist of spotty centrofacial pigmentation involving the vermilion border of the lips, the lacrimal caruncle, the conjunctival semilunar fold, and sometimes the sclera
lentigines, electrocardiogram conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness
LEOPARD syndrome
characterized by the classical triad of macrocephaly, genital lentiginosis, and intestinal polyposis
BANNAYAN-RILEY-RUVALCABA SYNDROME
also known as familial multiple CALMs and is autosomal dominant with mutations in the SPRED1 gene
Legius syndrome
- Multiple CALMs are present and axillary freckling and lipomas may be seen, but no neurofibromas are demonstrated.
- Macrocephaly and developmental delays are noted but are less severe than what is seen in neurofibromatosis Type 1
horizontal band of lentigines across the central face
hallmark of the autosomal dominant centrofacial lentiginosis syndrome
Other associated signs and symptoms include bone abnormalities, endocrine dysfunctions, neural tube defects, and mental retardation.
The presence of 6 or more CALMs larger than 5 mm in greatest diameter in prepubertal individuals or larger than 15 mm after puberty is one of the hallmarks of the disease
NEUROFIBROMATOSIS TYPE 1
pathognomonic for NF1
Intertriginous freckles
triad of poly/ monostotic fibrous dysplasia, CALMs, and hyperfunctioning endocrinopathies, including precocious puberty, hyperthyroidism, hypercortisolism, hypersomatotropism, and hypophosphatemic rickets
McCune-Albright syndrome
It is characterized by a growth deficiency, unusual facies, CALMs, and a sun sensitivity with telangiectasia and erythema that can result in atrophy and scarring.
BLOOM SYNDROME
- Bloom syndrome is a rare, autosomal recessive, genetic-immunodeficiency-and-cancer-predisposition syndrome
Neoplasias that occur frequently in Bloom syndrome
acute leukemia, lymphoma, and squamous cell carcinoma
- Cardinal features of the disease are low birth weight, short stature resulting from intrauterine and postnatal growth retardation, and a small triangular face.
- Other associated symptoms include clinodactyly of the fifth finger, relative macrocephaly, and facial, limb, or body asymmetry.
SILVER-RUSSELL SYNDROME
give conditions where Congenital circumscribed hypermelanosis with café-au-lait macules (CALMs) are seen
familial multiple CALMs (Legius syndrome), neurofibromatosis Type 1, McCuneAlbright syndrome, Bloom syndrome, Watson syndrome, and Silver-Russel syndrome
- clinical syndrome characterized by salt-wasting and diffuse cutaneous hyperpigmentation
- t is associated with adrenal insufficiency with inadequate secretion of corticosteroid and androgenic hormones, leading to compensatory overproduction of adrenocorticotropic hormone (ACTH) by the pituitary gland.
Addison disease
most striking cutaneous sign of patients with chronic Addison disease and is the consequence of ACTH binding to the melanocortin-1 receptor
Hyperpigmentation
- The hyperpigmentation occurs preferentially on sun-exposed areas (face, neck, hands), sites of trauma, scars, chronic pressure (knees, spine, knuckles, elbows, shoulders), in the palmar creases, nipples, areolae, axillae, perineum, and genitalia
comprises an enlarging pituitary tumor associated with elevated fasting plasma ACTH levels, hyperpigmentation, and neuroophthalmologic symptoms in patients with Cushing disease after bilateral adrenalectomy and inadequate hormonal replacement
NELSON SYNDROME
- chromaffin cell tumor of the adrenal medulla with associated excessive production of catecholamines.
- Pallor of the face resulting from vasoconstriction may be observed.
- In contrast, addisonian-like hyperpigmentation has been reported and is probably caused by ectopic ACTH and melanocyte-stimulating hormone production by the tumor.
- Pigmentation rapidly fades after surgical treatment
PHEOCHROMOCYTOMA
- Diffuse hyperpigmentation resulting from melanocytestimulating hormone–producing tumors, such as gastric or thymic carcinoid tumors,
- also can be accompanied by a pellagra-like rash occurring on light-exposed skin.
- the rash is secondary to a tryptophan deficiency, as a large amount of dietary tryptophan is diverted to serotonin by the tumor.
- Treatment of the underlying tumor is critical in the management of affected patientst
CARCINOID SYNDROME
- recently described entity noted in the African and Indian population in the fourth to fifth decades of life.
- It presents as dark-brown to black poorly demarcated areas of hyperpigmentation on the lateral forehead, temples, and zygoma
MATURATIONAL DYSCHROMIA
- Skin changes usually begin with hypopigmentation of the face.
- In areas exposed to friction and pressure, such as knees, elbows, and buttocks, hyperkeratoses and scaling in association with hyperpigmentation develop, giving the skin a “flaky paint” appearance.
- Hair may become hypopigmented. Sometimes there are bands of hypopigmentation along the hair shafts (flag sign), a result of periods of worse malnutrition.
KWASHIORKOR
Cobalamin or vitamin B 12 deficiency is caused by atrophic gastritis caused by what infection?
Helicobacter pylori infection
- an autoimmune process directed against gastric parietal cells, which lead to severe “intrinsic factor” deficiency (pernicious anemia).
- Blood examination reveals megaloblastic anemia and low levels of vitamin B1
Pellagra is caused by a deficiency of
niacin (vitamin B3)
Pellagra is characterized by the clinical triad of
dermatitis, dementia, and diarrhea
linear, sometimes flagellate hyperpigmentation can be observed in patients taking what medications?
bleomycin or zidovudine
hyperpigmentation on the palms and soles may be present in patients taking what drugs?
cyclophosphamide or doxorubicin
Diffuse slate-gray pigmentation also may be seen at the site of IV infusion of what drug?
iron infusion
can produce blue-gray pigmentation in photoexposed areas from accumulation of a lipidlike substance in macrophages.
Amiodarone
may give rise to a yellow-brown to bluish-gray pigmentation on the face, neck, lower extremities, and forearms after several years of intake, a result of deposition of a drug–melanin complex in the dermis
Chloroquine
The risk of minocycline-induced pigmentation increases with prolonged therapy at doses above what dose?
100 mg
Argyria patients present with a generalized grayish blue pigmentation caused by ingestion of what?
silver
This type of hyperpigmentation is often increased by ultraviolet exposure and is usually more pronounced in photoexposed areas.
Deposition of melanin in the dermis
Sometimes this type of pigmentation is accentuated in photoexposed areas, as ultraviolet light can induce a transformation in the deposited drug, which may then become more visible.
Direct deposition of the medication in the skin (eg, carotene, heavy metals)
Characteristic histologic appearance of ochronosis
yellow brown banana-shaped globules in the dermis
- Asymptomatic blue-black and gray-black hyperpigmented macules are characteristic and can be found on the face (malar, temples, lower cheeks), posterolateral neck, back, and extensor skin of the extremities.
- Later stages include progressive hyperpigmented colloid milium (“caviar-like lesions), papulonodular lesions, and areas of scarring
Ochronosis
most common cutaneous finding of Chikungunya
Pigmentary changes
- Lentiginous central facial hyperpigmentation, diffuse hyperpigmentation of acrofacial lesions, and flagellate hyperpigmentation have all been described.
- Striking pigmentation of the nose also has been reported.
- A maculopapular eruption is noted at the onset of the illness and resolves over 7 to 10 days.
exogenous ochronosis has been most frequently reported in association with what medications?
- hydroquinone, usually at concentrations greater than 4%
- phenol or resorcinol,
- quinine (antimalarial)
dermoscopy of ochronosis
Darkbrown globules and globular-like structures are seen on a diffuse brown background
They are abrupt changes from lighter to darker skin in a linear pattern mostly seen on the limbs, trunk, and face
Pigmentary demarcation lines (PDLs) are also known as Voigt or Futcher lines
■ Type A: This is the most common type and involves the lateral aspect of the upper anterior arms (occasionally extending across the pectoral area);
■ Type B: Posterior medial lower limb;
■ Type C: Vertical hypopigmented line in sternal and parasternal areas;
■ Type D: Vertical line in spinal or paraspinal area;
■ Type E: Hypopigmented oval areas, streaks, or bands on bilateral aspects of the chest, from the mid-third of clavicle to periareolar skin;
■ Type F: V-shaped hyperpigmented line between the malar prominence and the temple;
■ Type G: W-shaped hyperpigmented lines between the malar prominence and the temple; and
■ Type H: Linear hyperpigmentation from the angle of the mouth to the lateral aspect of the chin.
Oral ingestion of raw or insufficiently cooked what kind of mushroom is associated with a “flagellate mushroom dermatitis” that appears 12 hours to 5 days after consumption?
shiitake mushrooms
caused by frequent exposure to heat, usually infrared radiation, resulting in reticulate hyperpigmentation
ERYTHEMA AB IGNE
- Although it may occur anywhere on the body, it is usually localized to the thighs and lower legs
- Thyroid function tests should be considered in patients with symptoms or signs that suggest hypothyroidism.
■ Acquired diffuse reticulate pigmentation on the trunk.
■ Most common in young females.
■ Initial phase of pruritic papules, vesicles, and papulovesicles is followed by asymptomatic hyperpigmentation.
■ Tetracyclines and dapsone are helpful for the inflammatory component of the condition.
- The lesions develop on the upper back, chest, neck, and lumbosacral region.
- The papulovesicular lesions heal spontaneously over approximately 1 week, leaving nonpruritic reticular hyperpigmentation in its wake
- The eruption and pruritus respond well to** minocycline or doxycycline 100-200 mg daily or dapsone 25 to 100 mg daily**. The pigmentation resolves spontaneously.
Prurigo pigmentosa
■ Acquired circumscribed hyperpigmentation in the form of symmetrical pinhead-sized macules on the malar region of the face.
■ Noted mainly in Asian populations.
■ Often coexists with other pigmentary conditions like melasma and flat seborrheic keratoses.
■ Best treated with quality-switched Nd:YAG lasers.
NEVUS OF HORI
pathogenesis of Hori Nevus that has been suggested as being the most plausible mechanism with ultraviolet radiation and sex hormones as activating factors
reactivation of preexisting latent or immature dermal melanocytes
other:
(a) “dropping” of epidermal melanocytes into the dermis,
(b) migration of melanocytes from hair bulbs
In many cases, Nevus of Hori or acquired bilateral nevus of Ota–like macules (ABNOM) or acquired dermal melanocytosis can occur simultaneously with other pigmentary abnormalities such as ?
melasma, freckles, solar lentigines, and nevus of Ota.
- This benign hamartoma may be cosmetically disfiguring and presents with a hyperpigmented macular or speckled area, most commonly in the scapular region, upper arms and chest, although it has been described in any area of the body.
- Hypertrichosis is common and often develops years after the hyperpigmentation is noted.
- The hairs are coarse and dark. Becker nevi are often first noted after an episode of intense sun exposure.
Nevus of Becker
Associated anomalies, such as ipsilateral breast hypoplasia, musculoskeletal abnormalities (eg, scoliosis, ipsilateral limb hypoplasia), maxillofacial abnormalities, and additional cutaneous hypoplasias, occur in the rare nevus of Becker syndrome.
Ephelides are inherited in what pattern?
autosomal dominant
gene mutated in ephelides
MCR-1 gene
- Diffuse brown hyperpigmentation is noted in newborns or during the first few weeks of life and is located on **acral and or perineal areas. **
- Progression to the trunk, oral mucosal involvement, and seizures were reported in one case
- Spontaneously resolves.
ACROMELANOSIS PROGRESSIVA
remains the gold standard treatment in PIH
POSTINFLAMMATORY HYPERPIGMENTATION
PIH after epidermal inflammation results in ____ discoloration while inflammation in the dermis results in a ________ discoloration
PIH after epidermal inflammation results in brown discoloration while inflammation in the dermis results in a gray-brown discoloration
remains the gold standard treatment of melasma
Hydroquinone
hydroquinone MOA
Tyrosinase inhibitor
Retinoids MOA
Stimulate keratinocyte turnover, reduce melanosome transfer, tyrosinase inhibitor
Arbutin MOA
Tyrosinase inhibitor; inhibits melanosome maturation
Azelaic acid MOA
Tyrosinase inhibitor
Kojic acid MOA
Interacts with copper and inhibits tyrosinase
Tranexamic acid MOA
Plasmin inhibition; antioxidant
most commonly affected areas in melasma
malar and mandibular regions, forehead, chin, and upper lip are most commonly affected
Melasma spares the periorbital skin as well as the lips, neck, and ears. It may be seen less commonly on the forearms (also known as acquired brachial cutaneous dyschromatosis).
most common pattern of melasma
- centrofacial (63%: forehead, nose, chin, and upper lip);
- malar (21%: nose and cheeks); and
- mandibular (16%: ramus mandibulae)
components of Kligman’s formula
5% hydroquinone, 0.1% tretinoin, and a mild topical corticosteroid
triple combination therapy
4% hydroquinone, 0.05% tretinoin, and a topical corticosteroid
- characterized by numerous lentigines with sharp margins.
lesions occur in a segmental pattern in the midline in 1 or more dermatome
PARTIAL UNILATERAL LENTIGINOSIS
- It is characterized by rapid onset of a reticular graybrown to almost black reticulate hyperpigmentation.
- The face (especially the forehead, zygomatic area, and temples) and the neck are principally involved, but the hands, forearms, and trunk also may be affected
- Inflammatory findings, such as erythema and pruritus, are usually absent although it may be observed in very early stages of the clinical course.
Riehl melanosis
- has been postulated to be induced by repeated contact with threshold doses of a contact sensitizer such as fragrances, some pigments, and bactericides used in cosmetics and optical whiteners
- initially presents with brown macules and patches noted on the **palms and soles. **
- This is followed by **generalized pigmentary changes **with onychodystrophy and alopecia
- GI symptoms, such as abdominal pain, nausea, diarrhea, and loss of weight, are noted in addition to GI polyposis and occasional malignancies
- may be associated with other autoimmune conditions like systemic lupus erythematosus and rheumatoid arthritis
Cronkhite-Canada syndrome
Erythema followed by diffuse light-brown to darkbrown pigmentation in the perioral region affecting the cutaneous upper and lower lip with sparing around the** vermilion border** is usually seen. In some cases, scale and loss of vellus hairs are noted.
ERYTHROSE PERIBUCCAL OF BROCQ
- presents with widespread asymptomatic welldemarcated blue-gray macules that are most commonly seen on photoprotected sites
- Lesions slowly expand over time and an erythematous border may be seen at the edge of the lesion in the acute stages of the condition
- The erythematous border, especially in darker-skin types, may evolve into a hypopigmented border that accentuates the hyperpigmentation.
Erythema dyschromicum perstans (EDP)
■ Acquired idiopathic dermal melanosis.
■ Poorly demarcated brown to gray-brown hyperpigmented macules. Symmetrical brown to gray-brown poorly demarcated macules and patches are seen mainly in photoexposed sites such as the head (forehead and temples) and neck
■ Usually seen with deeply pigmented skin (eg, South East Asians, Arabic).
■ Mostly in photoexposed sites.
■ Treatments provide only minimal improvement in pigmentation.
LICHEN PLANUS PIGMENTOSUS
■ Acquired idiopathic dermal melanosis.
■ Eruption of asymptomatic, well-demarcated, nonscaly, brown macules and plaques (5 mm to several centimeters in diameter) involving the face, neck, trunk, and proximal extremities.
■ Usually smaller lesions than erythema dyschromicum perstans.
■ Usually appears in children and adolescents.
■ Treatments provide only a minimal improvement in pigmentation.
IDIOPATHIC ERUPTIVE MACULAR HYPERPIGMENTATION
- rare autosomal dominant disorder (mutation in the ABCB6 gene on chromosome 12q21-q23) that usually presents in infancy or early childhood in Japanese families and is characterized by pinpoint to pea-sized hypopigmented and hyperpigmented macules, distributed in a reticulated pattern over the trunk, abdomen, and limbs, usually sparing the face and palmoplantar surfaces
DYSCHROMATOSIS HEREDITARIA UNIVERSALIS
- localized form of dyschromatosis universalis hereditaria, also called dyschromatosis symmetrica hereditaria.
- It is characterized by small, symmetric, hyperpigmented and hypopigmented macules on the** dorsal hands and feet, **and is mainly seen in young children in South American and Asian families
RETICULATE ACROPIGMENTATION OF DOHI
- condition **found in persons living in poor hygienic conditions. **
- Many abuse alcohol, live on an inadequate diet, and are infested with lice and/or scabies.
- Diffuse light-brown hyperpigmentation is present at the shoulder and waist girdle, and the neck and back are dotted with depigmented macules.
- The condition improves upon institution of a healthier lifestyle and likely represents a coexistence of many disorders
VAGABOND LEUKODERMA
