Hyperpigmentation Flashcards
Top 6 inflammatory causes of PIH
Acne Atopic dermatitis Impetigo Insect bites LSC TNPM
Associations with ashy dermatosis
- Infectious: HIV, whipworm
- Medications: benzodiazepine, penicillins, oral x-ray contrast media, ammonium nitrate
- Endocrinopathies: thyroid disease
- Chemicals: exposure to pesticides, fungicides, toxins
How is ashy dermatosis different to LPP
Ashy dermatosis: cleavage lines, has erythematous border, trunk most commonly, slate-gray to blue brown
LPP is sun exposed: forehead, temples, neck, intetriginous zones, no erythematous border
The histo is different too
Types of melasma
Epidermal
Dermal
Mixed
Indeterminate
Clinical presentation of melasma
- Centrofacial - forehead, cheeks, nose, upper lip, chin but spares the philtrum and nasolabial folds
- Malar: cheek and nose
- Mandibular: along the jawline
What is Riehl melanosis
Pigmented contact dermatitis - dermal melanin depositis
Topical treatment for melasma - the combination treatment
4% HQ + kojic acid 4% + tranexamic acid 4% + hydrocortisone 4% (what katie uses) + tretinoin 0.025%
Tranexamic acid CI and A/E and dosage
- CI: stroke, spontaneous abortion, smoking, cancer, cardiovascular
- A/E: headaches, menstrual irregularity, nausea
250 mg BD
Common drugs that cause hyperpigmentation
Chemo: bleomycin, cyclophosphamide, 5-FU, hydroxyurea, MTX Anti-malarials: chloroquine, quinacrine, hydroxychlorquine Heavy metals: arsenic, gold, iron Hormones: OCP, afemalotide Other: amiodarone clofazamine Diltiazem and amlodipine Hydroquinone Minocycline
Minocycline induced hyperpigmentation
Type 1: blue-black discolouration in sites of inflammation and scars, including acne or ablative laser
Type 2: blue-gray macules/patches (1mm-10 cm) within previously normal skin, most often on the shin, sometimes misdiagnosed as ecchymoses
Type 3: diffuse, muddy brown pigment most prominent in sun exposed areas
Blue-black discolouration may also involve nails, sclerae, oral mucosa, bones, thyroid and teeth.
Ochronosis
From hydroquinone
Hyperpigmentation in areas of application due to ICD or exogenous ochronosis - latter can produce small, caviar like papules
In ochronosis: yellow-brown banana-shaped fibres in the papillary dermis
Metabolism of melanocytes of hydroquinone into ringed structures that serve as precursors of ochronotic fibres. May fade upon discontinuation of hydroquinone, variable improvement with lasers
Dilitazem and amlodipine induced hyperpigmentation
Slate gray to gray-brown discolouration of sun-exposed skin in patients, peri-follicular accentuation, and a reticular pattern may be observed.
Sparse lichenoid infiltrate and numerous dermal melanophages
Clofazimine induced hyperpigmentation
Diffuse red to red-brown discolouration of skin, conjunctivae. Violet-brown to blue-gray discolouration, especially of lesional skin.
Red colour secondary to drug in fat, blue-violet colour secondary to brownish granular pigment within dermal macrophages.
EM: phagolysosomes contain amorphous granular material and lamellar structures, characteristic of lipofuscin.
Fades gradually after discontinuation
Amiodarone induced pigmentation
Slate-gray to violaceous discolouration of sun exposed skin, face.
Occurs in fair-skinned patients after long-term, continuous therapy.
On histo yellow-brown granules in dermal macrophages, mostly in a perivascular distribution.
By EM, lysosomal inclusions composed of a lipid-like substance. Usually fades completely over months to years after finishing the drug, but sometimes it can persist
Arsenic cutaneous signs
PPK
SCC
Arsenic
Bronze hyperpigmenation, can have superimposed raindrops of lightly pigmented skin. Axillae, groin, palms, soles, nipples and pressure points.
Appears 1-20 years after arsenic exposure.
Palmoplantar keratoses and SCC
Dermal and epidermal deposition of arsenic, increased epidermal melanin synthesis
Chloroquine, hydroxychloroquine, quinacrine hyperpigmentation
Gray to blue-black pigment, usually pre-tibial with HCQ.
Face, hard palate, sclerae and subungual areas.
Quinacrine: diffuse yellow to yellow-brown discolouration
Discolouration affects up to 25% of patients
Dermal deposition of melanin-drug complexes, haemosiderin around capillaries. May fade after discontinuation of drug, but rarely resolves completely.
5-FU Hyperpigmentation
5-FU
Hyperpigmentation in sun-exposed areas - ~5% of patients treated systematically, often follows an erythematous photosensitivity reaction
Increased pigmentation over skin in which vein had been infused
Also includes dorsal aspects of hands, palms/soles and radiation ports
Transverse of diffuse melanonychia, lunular pigmentation
Leaves PIH
Cyclophosphamide hyperpigmentation
Diffuse hyperpigmentation of skin and mucous membranes, Transverse, longitudinal or diffuse melanonychia, and pigment can be on palms, soles or teeth.
Usually regresses 6-12 months after therapy has discontinued
Ddx for diffuse hyperpigmentation
With sclerodermoid: SScl, POEMS, PCT Medication induced Hyperthyroidism Haemochromatosis Addison disease, Cushing Renal disease Nutritional: pellagra, B12 deficiency, folate deficiency, malabsorption At birth: CAH, carbon baby syndrome, familial diffuse melanosis
Where are pigmentary demarcation lines
- Anterolateral portion of the upper arm
- Posteromedial aspect of thighs
- Upper chest
- Paraspinal region of the back
- Face
Ddx for linear hyperpigmentation
Blaschkoid: Inherited: - IP third stage - Linear and whorled naevoid hypermelanosis - Goltz syndrome - McCune albright - Epidermal naevus - Conradi Hunermann Acquired - Linear LP - LPP - Ashy dermatosis - Linear atrophoderma of Moulin - PIH due to Blaschkitis
Non-blaschkoid:
- Flagellate erythema
- Phytophotodermatitis
- Linear nigra
- Linear PIH
Flagellate erythema of bleo
1-9 weeks after starting
- Circumscribed: typically over the joints or in other pressure points, but hyperpigmentation can be localized to the palmar creases, striae or sites of adhesive electrode pads
- Occurs after cumulative doses of 100-300 mg, however has been as low as 15-30 mg (following wart injection etc)
- Some patients have pruritus or linear urticarial lesions preceding the pigmented streaks, but some people have no itch
- Brown, commonly on chest and back
- Other cutaneous findings with bleomycin:
- Painful nodules on fingers
- Verrucous plaques on knees and elbows
- Sclerodermoid changes
- Digital gangrene due to Raynauds
- Nails: melanonychia, Beau’s lines, onychomadesis, onycholysis
Flagellate erythema of mushrooms
- Pruritic erythematous papules, vesicles and oedema on face, scalp, trunk and extremities
- 1-2 days post ingestion
- Scratching –> long, flagellate streaks composed of erythematous papules and/or petechiae on the extremities and the trunk, sparing the mid-upper back
- Can be followed by a linear pattern of either discolouration due to haemosiderin or PIH
- Diffuse erythema and oedema in photoexposed areas have been observed in half of Japanese patients, with shiitake mushroom dermatitis
- Fever and malaise are also associated
Linear and whorled naevoid hypermelanosis extra-cutaneous features
- Extra-cutaneous: 10-25%
- Neurologic
- Musculoskeletal
- Cardiac (less often)
Dental
Ocular
Dysmorphism
Ddx for reticulate hyperpigmentation
Not genetic CARP Prurigo pigmentosa Erythema ab igne Pityriasis Atopic dirty neck Drug induced
Genetic:
- Dyskeratosis congenita
- Dowling Degos
- Galli Galli
- others
Prurigo pigmentosa associations and clinical
Pathogenesis
- Ketotic states: diabetes, fasting, post-bariatric
- Systemic diseases: Sjogren
- Eating disorders: anorexia nervosa
- Described in atopy and pregnancy too
Clinical
- Pruritic erptuion of erythematous papules and papulovesicles on back, neck and chest
- Crops of inflammatory lesions develop rapidly and then involute within a week leaving macular reticulated hyperpigmentation
- Recurrences occur at same site
- Lesions in multiple stages are evident
Prurigo pigmentosa histology
Stages:
- Neutrophilic: Neutrophilic exocytosis, spongiosis, papillary dermal oedema, superficial perivascular neutrophilic infiltrate
- Eosinophilic: Intra or subepidermal vesiculation, necrotic keratinocytes, patchy lichenoid infiltrate of predominantly lymphocytes admixed with eosinophils
- Variable parakeratosis, acanthosis, hyperpigmentation of epidermis as well as dermal melanophages
Prurigo pigmentosa treatment
- Oral minocycline, doxycycline, or dapsone –> neutrophilic seems to work
- Doesn’t respond to topical steroids
Triad for dyskeratosis congenita
Genetically heterogeneous disorder caused by defective telomere maintenance. Characterised by progressive bone marrow failure, and triad of:
- Reticulated hyperpigmentation
- Nail dystrophy
- Leukoplakia
Dyskeratosis congenita epidemiology
- Most common: X-linked recessive
- Can be autosomal dominant and recessive
- M>F 3:1
DKC1 mutation + others
Dyskeratosis congenita clinical
DYSKERATOSIS Dicks and dominant Y Skeletal: bone marrow failure K Epiphora: continueous lacrimation Resp: fibrosis, liver cirrhosis Avascular necrosis fo the femoral head Tumours: SCC, myelodysplastic syndrome, AML, GI cancers Oesophageal or urerthral senosis Short stature, developmental delay Immunologic dysfunction leading to opportunistic infection Sweating - hyperhidrosis, hyperkeratosis
Cutaneous: hyperpigmentation Oral leukoplakia Nail dystrophy: pterygia Graying of hair prematurely E N I Telangiectasia – poikiloderma atrophicans vasculare Acrocyanosis
Clinical
- Cutaneous:
- lacy, reticulated pattern of hyperpigmentation in the first decade of life. This occurs to neck, upper chest, and upper arms, sometimes with macules of hypopigmentation
- Telangeictasia and epidermal atrophy –> poikiloderma atrophicans vasculare
- Wrinkled skin on the extremities, dorsal aspects of hands and genitals
- Palmoplantar hyperhidrosis and hyperkeratosis
- Loss of dermatoglyphs
- Frictional bullae
- Acrocyanosis
- Premature graying of the hair
- Nail dystrophy
- Present during early childhood
- Initial changes: longitudinal ridging and splitting, followed by pterygia formation, and occasionally complete nail loss
- Oral
- Pre-malignant leukoplakia, usually occurring in early adolescence
- White plaques have predilection for lateral portion of tongue
- Can have involvement of urethra, vagina and anus
- Can have teeth malformation, missing, aberrant spacing or extensive caries
- Extra-cutaneous
- Epiphora: continuous lacrimation due to lacrimal duct atresia
- Bone marrow failure: 50-90%, major cause of mortality
- Second-third decade
- Anaemia, thrombocytopaenia, pancytopaenia
- Malignancies:
- Third-fourth decade
- SCCs in mouth, anus, cervix, vagina, oesophagus, skin’
- Increased risk of myelodysplastic syndrome, AML and GI carcinomas
- Other
- Pulmonary fibrosis
- Liver cirrhosis
- Developmental delay
- Short stature
- Avascular necrosis of the femoral head
- Oesophageal or urethral stenosis
- Cryptorchidism
- Male hypogonadism
- Immunologic dysfunction leading to opportunistic infection
Can diagnose with FISH
Dowling Degos mutation
KRT5
Dowling Degos clinical
- Third-fourth decade of life
- Reticulated hyperpigmentation with sometimes lentigo-like brown macules, small brown papules with variable hyperkeratosis
- Findings progressively increased over time
- Start in axillae and groin, followed by intergluteal and inframammary folds, neck, trunk, inner aspect of arms and thighs
- Pruritis can occur
- Comedone-like lesions on the back or neck, pitted perioral scars, epidermoid cysts and HS represent additional features
Dermnet says:
- Hyperpigmentation
- Follicular papules
- Hypopigmented macules and papules
- Comedones predominantly to neck
- Scar
Associations:
- HS
- SCCs and KAs
- Nail dystrophy
- Seb Ks
- Cysts
Dowling Degos histology
- Increased pigmentation of the basal layer and finger-like elongation of the rete ridges within thinning of the suprapapillary epithelium - antler like pattern
- Dermal melanophages, mild perivascular lymphohistiocytic infiltrate
- Galli-Galli disease - variant, suprabasal non-dyskeratotic acantholysis of lesional skin, also KRT5 mutation
Dowling Degos treatment
No successful treatmentsTopical steroids, retinoids, azelaic acid
Er:Yag
