Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and pathological aspects of Laugier-Hunziker syndrome

Table 1 Geographical distribution of published cases affected with Laugier-Hunziker syndrome

	Country	No. of cases	Percentage (%)	Ref.
1	France	59	29	[1,14,20-22,24,26,27,30,31]
2	Italy	33	16	[11,12,18,25,28,29,33,34-37,40,63]
3	China	30	14.5	[5,9,10,19,23,58,72]
4	United States	14	7	[13,16,32,42,46,51,60,67-69,73,77,85,88]
5	United Kingdom	13	6	[3,39,45,49,52,54,76]
6	Germany	12	6	[40,61]
7	India	8	4	[47,56,57,70,71,81,86]
8	Turkey	6	3	[7,50,53,62,75,83]
9	Greece	5	2	[6,40,48]
10	Japan	5	2	[8,44,55,59]
11	Lebanon	3	1.5	[17]
12	Portugal	2	1	[23,43]
13	Brazil	2	1	[65,78]
14	Spain	2	1	[66]
15	Australia	2	1	[87]
16	Finland	1	0.5	[4]
17	Ireland	1	0.5	[15]
18	Russia	1	0.5	[38]
19	Switzerland	1	0.5	[41]
20	South Korea	1	0.5	[64]
21	Austria	1	0.5	[74]
22	Serbia	1	0.5	[79]
23	Chile	1	0.5	[80]
24	Romania	1	0.5	[82]
25	Singapore	1	0.5	[84]

Table 2 Distribution of involved locations of pigmentary lesions in Laugier-Hunziker syndrome

Involved locations		Frequency	Ref.
Lip		75% (154/206)	[1,3-16,18,19,21-25,27-29,31-38,40,41,43-52,54-68,70-73,75-78,80,83,85-88]
Oral cavity		68% (140/206)	[1,3-9,11-19,21-24,26,27,29,31-33,35-44,46,47,50-60,62-76,78,79,81,82,84-88]
Acral area	Nail	47% (96/206)	[1,3-10,12,14-17,19,22,23,25-27,31,32,34,39-41,43,44,47,49,50,52-54,56-59,61,63-66,68-72,77-84,86]
	Periungual area	8% (17/206)	[8,14,16,25,31,34,43,47,50,54,64,65,71,73,77,79,81]
	Finger	13% (26/206)	[5,8,9,11,14,19,21,41,43,49,55-57,59,60,66,70-72,74,76,84-86,88]
	Palm	4% (8/206)	[7,43,44,46,59,60,62,81]
	Toes	3% (6/206)	[19,56,59,70,84,86]
	Sole	3% (6/206)	[7,21,46,59,62]
Genitalia	Penis	24% (17/70)1	[20-23,46]
	Vulva or labia majora	10% (13/127)1	[7,12,15,17,21,30,58,74]
Anal mucosa and perianal area		1.5% (3/206)	[21,41]
Conjunctiva and sclera		4% (9/206)	[6,7,17,19,23,46,60,83]
Eyebrow and periorbital area		1.5% (3/206)	[41,53,71]
Pharynx		0.5% (1/206)	[4]
Esophagus		0.5% (1/206)	[44]
Neck, thorax, and abdomen		1% (2/206)	[25,81]
Back		0.5% (1/206)	[50]
Elbow		1% (2/206)	[43,76]
Pretibial area		0.5% (1/206)	[62]

¹Frequency of genitalia involvement of pigmentation was assessed according to the known sum of male or female cases.

Table 3 Various conditions associated with labial or oral pigmentation

	Focal	Diffuse
Exogenous origin	Amalgam tattoo	Tobacco-associated melanin pigmentation
		(smoker’s melanosis)
	Topical medications	Drugs (e.g., antimalarials, tetracyclines, ketoconazole, zidovudine, phenothiazines, oral contraceptives, and chemotherapeutic agents)
	Graphite tattoo (e.g., carbon, lead pencils)	Heavy metals (including bismuth, mercury, silver, lead, gold, arsenic, tin, copper, brass, zinc, cadmium, chrome, and manganese)
Endogenous origin	Melanotic macule	Physiologic (racial) pigmentation
	Melanocytic nevus	Posttraumatic or postinflammatory pigmentation
	Melanoacanthoma	Lichen planus
	Melanoma	Discoid lupus erythematosus
	Hemangioma	LHS
	Lentigo maligna	Peutz-Jeghers syndrome
	Kaposi sarcoma	Addison’s disease
		McCune-Albright syndrome
		Neurofibromatosis type 1 (von Recklinghausen’s disease)
		Carney complex (NAME/LAMB syndrome)
		LEOPARD syndrome (lentiginosis profusa syndrome)
		Cronkhite-Canada syndrome
		Cushing syndrome
		Incontinentia pigmenti syndrome (Bloch-Sulzberger syndrome)
		Acanthosis nigricans
		Dyschromatosis symmetrica hereditaria
		Tuberous sclerosis
		Xeroderma pigmentosum
		Dyskeratosis congenita
		Hemochromatosis
		Fanconi anemia

Table 4 Differential diagnosis between Peutz-Jeghers syndrome and Laugier-Hunziker syndrome

	PJS	LHS
Inheritance	Autosomal dominant (STK11 gene)	Sporadic and acquired
Age of onset	Birth to infancy	Adult onset
Shape of mucocutaneous pigmented macules	Freckle-like	Lenticular
Labial pigmentation	Very common	Very common
Oral pigmentation	Common	Very common
Perioral, perirhinal, or periorbital pigmentation	Common	Uncommon
Nail pigmentation	Uncommon	Very common
Acral skin pigmentation	Common	Common
Systemic involvement	Gastrointestinal polyposis	None
Risk of malignancy	Colon, gastric, small intestinal, pancreatic, breast, ovarian, thyroid, lung, and Sertoli cell (in men) cancers	None

PJS: Peutz-Jeghers syndrome; LHS: Laugier-Hunziker syndrome.

Table 5 Differential diagnosis of nail pigmentation

Causation of nail pigmentation		Condition
Nonmelanocytic origin	Exogenous	Dirt
		Tobacco
		Tar
		Potassium hypermanganate
		Silver nitrate
	Infectious	Bacterial infection
		(e.g., Pseudomonas aeruginosa)
		Onychomycosis
		(fungal infection)
	Traumatic	Subungual hemorrhage
		Subungual hematoma
	Neoplastic	Hemangioma
Melanocytic origin	Physiological	Ethnic (racial) melanonychia
	Nutritional	Vitamin B12 deficiency
	Traumatic	Onychotillomania (nail biting)
		Frictional melanonychia
	Iatrogenic	Systemic drug-induced melanonychia
		(e.g., zidovudine, hydroxyurea, and minocyline)
		Radiotherapy-induced melanonychia
	Inflammatory	Lichen planus
		Psoriasis
	Endocrinic	Addison’s disease
		Pregnancy
	Syndromic	LHS
		AIDS
	Activated melanocytic	Benign melanocytic hyperplasia
		Lentigo simplex
		Nevus
	Neoplastic	Onychopapilloma
		Onychomatricoma
		Bowen’s disease
		Melanoma

LHS: Laugier-Hunziker syndrome; AIDS: Acquired immunodeficiency syndrome.