Hyperpigmentation

Question 1

Top 6 inflammatory causes of PIH

Answer 1

Acne
Atopic dermatitis
Impetigo
Insect bites
LSC
TNPM

Question 2

Associations with ashy dermatosis

Answer 2

• Infectious: HIV, whipworm
• Medications: benzodiazepine, penicillins, oral x-ray contrast media, ammonium nitrate
• Endocrinopathies: thyroid disease
• Chemicals: exposure to pesticides, fungicides, toxins

Question 3

How is ashy dermatosis different to LPP

Answer 3

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

Question 4

Types of melasma

Answer 4

Epidermal
Dermal
Mixed
Indeterminate

Question 5

Clinical presentation of melasma

Answer 5

1. Centrofacial - forehead, cheeks, nose, upper lip, chin but spares the philtrum and nasolabial folds
2. Malar: cheek and nose
3. Mandibular: along the jawline

Question 6

What is Riehl melanosis

Answer 6

Pigmented contact dermatitis - dermal melanin depositis

Question 7

Topical treatment for melasma - the combination treatment

Answer 7

4% HQ + kojic acid 4% + tranexamic acid 4% + hydrocortisone 4% (what katie uses) + tretinoin 0.025%

Question 8

Tranexamic acid CI and A/E and dosage

Answer 8

• CI: stroke, spontaneous abortion, smoking, cancer, cardiovascular
• A/E: headaches, menstrual irregularity, nausea
  250 mg BD

Question 9

Common drugs that cause hyperpigmentation

Answer 9

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

Question 10

Minocycline induced hyperpigmentation

Answer 10

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.

Question 11

Ochronosis

Answer 11

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

Question 12

Dilitazem and amlodipine induced hyperpigmentation

Answer 12

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

Question 13

Clofazimine induced hyperpigmentation

Answer 13

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

Question 14

Amiodarone induced pigmentation

Answer 14

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

Question 15

Arsenic cutaneous signs

Answer 15

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

Question 16

Chloroquine, hydroxychloroquine, quinacrine hyperpigmentation

Answer 16

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.

Question 17

5-FU Hyperpigmentation

Answer 17

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

Question 18

Cyclophosphamide hyperpigmentation

Answer 18

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

Question 19

Ddx for diffuse hyperpigmentation

Answer 19

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

Question 20

Where are pigmentary demarcation lines

Answer 20

• Anterolateral portion of the upper arm
  
  • Posteromedial aspect of thighs
  • Upper chest
  • Paraspinal region of the back
  • Face

Question 21

Ddx for linear hyperpigmentation

Answer 21

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

Question 22

Flagellate erythema of bleo

Answer 22

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

Question 23

Flagellate erythema of mushrooms

Answer 23

• 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

Question 24

Linear and whorled naevoid hypermelanosis extra-cutaneous features

Answer 24

• Extra-cutaneous: 10-25%
  
  • Neurologic
  • Musculoskeletal
  • Cardiac (less often)
    Dental
    Ocular
    Dysmorphism

Question 25

Ddx for reticulate hyperpigmentation

Answer 25

``` Not genetic CARP Prurigo pigmentosa Erythema ab igne Pityriasis Atopic dirty neck Drug induced ``` Genetic: - Dyskeratosis congenita - Dowling Degos - Galli Galli - + others

Question 26

Prurigo pigmentosa associations and clinical

Answer 26

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

Question 27

Prurigo pigmentosa histology

Answer 27

Stages: 1. Neutrophilic: Neutrophilic exocytosis, spongiosis, papillary dermal oedema, superficial perivascular neutrophilic infiltrate 2. Eosinophilic: Intra or subepidermal vesiculation, necrotic keratinocytes, patchy lichenoid infiltrate of predominantly lymphocytes admixed with eosinophils 3. Variable parakeratosis, acanthosis, hyperpigmentation of epidermis as well as dermal melanophages

Question 28

Prurigo pigmentosa treatment

Answer 28

- Oral minocycline, doxycycline, or dapsone --> neutrophilic seems to work - Doesn't respond to topical steroids

Question 29

Triad for dyskeratosis congenita

Answer 29

Genetically heterogeneous disorder caused by defective telomere maintenance. Characterised by progressive bone marrow failure, and triad of: 1. Reticulated hyperpigmentation 2. Nail dystrophy 3. Leukoplakia

Question 30

Dyskeratosis congenita epidemiology

Answer 30

- Most common: X-linked recessive - Can be autosomal dominant and recessive - M>F 3:1 DKC1 mutation + others

Question 31

Dyskeratosis congenita clinical

Answer 31

``` 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

Question 32

Dowling Degos mutation

Answer 32

KRT5

Question 33

Dowling Degos clinical

Answer 33

- 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: 1. Hyperpigmentation 2. Follicular papules 3. Hypopigmented macules and papules 4. Comedones predominantly to neck 5. Scar Associations: - HS - SCCs and KAs - Nail dystrophy - Seb Ks - Cysts

Question 34

Dowling Degos histology

Answer 34

- 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

Question 35

Dowling Degos treatment

Answer 35

No successful treatmentsTopical steroids, retinoids, azelaic acid Er:Yag