AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Background

Laugier-Hunziker syndrome (LHS) was initially described in 1970 as acquired, benign hyperpigmentated macules of the lips and buccal mucosa frequently associated with longitudinal melanonychia. Extended mucocutaneous features have been observed since that original description, including macular pigmentation of the genitalia. No underlying systemic abnormalities are associated with LHS, and no malignant predisposition exists. This lack of somatic abnormalities has moved some authorities to propose a name change to Laugier and Hunziker pigmentation.¹ When associated with nonclassic body locations or atypical features, the name idiopathic lenticular mucocutaneous hyperpigmentation has been used.²

Pathophysiology

The etiology of melanosis in LHS is unknown. A lack of family members with LHS is characteristic in most cases. To date, only one case of familial LHS has been described, which involved a mother and 2 daughters.³ Environmental risk factors have not been identified.

Frequency

United States

The incidence is rare, but it is likely underreported. Three patients, including 1 white female and 2 Hispanic females, have been described in the United States.

International

The prevalence appears to be higher in France and Italy when compared with the United Kingdom and the United States. Worldwide, approximately 60 cases were reported from 1970-1991. Among the patients described prior to 1989, 27 (93%) of 29 patients were from continental Europe. To date, more than 100 cases have been described.⁴

Mortality/Morbidity

Systemic illness and malignancy are not features of LHS. Such findings in association with mucocutaneous melanotic hyperpigmentation exclude the diagnosis of LHS.

Race

• LHS mainly affects whites; however, persons of Hispanic, Arabic, or Asian⁵ descent have been described.
• Idiopathic buccal melanosis without longitudinal melanonychia is a normal finding in 38% of black patients and in 5% of white patients. Physiologic melanoplakia, a term also used to describe idiopathic racial or ethnic melanosis, is most commonly noted on the gingiva of individuals with darker skin types. The histopathologic features of LHS are indistinguishable from those of physiologic melanoplakia.
• Longitudinal melanonychia (also known as melanonychia striata) without associated mucosal melanotic macules is a normal finding in 77% of blacks by age 20 years, and it is seen in 90% of blacks by the fifth decade of life. It most commonly occurs on the thumbs, with onset often during infancy or puberty.

Sex

• LHS was initially predominantly thought to affect females, with an estimated female-to-male ratio of 2:1. However, the idea that LHS is equally distributed between the sexes is gaining popularity.⁴

Age

• Essential melanotic pigmentation typically develops during early to middle adulthood, in persons aged 20-40 years, but it can occur as late as the sixth or seventh decade of life. A mean age of 52 years⁶ and a median age of 42 years⁷ have been reported.
• Physiologic (racial or ethnic) melanosis characteristically occurs during the first 3 decades of life.
• Peutz-Jeghers syndrome (PJS), a major differential diagnosis of LHS, usually has its onset at birth or during the first few years of life. However, sporadic cases of PJS have been reported in as many as 40% of cases, and it can have a late onset. See Peutz-Jeghers Syndrome for more information on this syndrome. Additionally, the Medscape CME course Hamartomatous Polyposis Syndromes may be of interest.

CLINICAL

Section 3 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Physical

• Oral pigmentation^{8, 9, 10} is most commonly present on the buccal mucosa and the lips (usually the lower lip), but it can also occur on the gingiva, the tongue, the soft palate, and the hard palate. Macules are brown, black, or slate with a smooth surface. They may be solitary or confluent. Round, lenticular, and linear lesions have been described, and they may be well defined or indistinct. On average, the macules are 5 mm or smaller; however, buccal lesions as large as 1 cm have been described. Oral hyperpigmentation may exist alone or in combination with nail and/or skin pigmentation. Of the 5 cases originally described by Laugier and Hunziker, 40% had oral involvement only. Subsequent reports have also described the onset of oral pigmentation following melanonychia.
• Nail hyperpigmentation^{11, 12, 13} occurs in an estimated 60% of cases, and it is permanent. Typically, multiple nails from both the fingers and the toes are involved. The degree of pigmentation may vary between streaks on the same patient. Streaks are smooth and not associated with dystrophic changes. The following 4 pigmentary presentations have been described:
• • One longitudinal band per nail, 1-8 mm in thickness
  • Two longitudinal bands per nail, 1-8 mm in thickness, which tend to occur along the lateral aspects of the nail plate
  • Half nail pigmentation
  • Complete nail pigmentation
• The Hutchinson sign, defined as the extension of pigment onto the proximal nail fold, is characteristically believed to be an ominous finding associated with spreading malignant melanoma. However, a pseudo-Hutchinson sign has been reported in multiple patients with LHS,^{14, 15} sometimes on various nails of the same patient. Pigment may also involve the lateral nail folds.
• Extended mucocutaneous pigmentation has become a recognized feature of LHS.¹⁶ Melanotic macular hyperpigmentation has been observed on the neck, the thorax, the abdomen, the dorsal and lateral aspects of the fingers, the palms and soles, the genitalia, the perineum, the perianal skin, and the anal mucosa of patients with LHS. Patients with LHS involving the conjunctiva, sclera, and esophageal mucosa have also been reported.^{1, 3, 17}

Causes

The etiology of melanosis in LHS is unknown.

DIFFERENTIALS

Section 4 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Other Problems to be Considered

Amalgam tattoo
Contact mucositis
Chemicals and/or minerals (eg, arsenic, fluoride)
Drug-induced hyperpigmentation
Friction-induced longitudinal melanonychia of the toenails
Heavy metal exposure
Infection
Malnutrition (eg, vitamin B-12 deficiency)¹⁸
Peutz-Jeghers syndrome
Physiologic melanoplakia and melanonychia
Smoking (ie, Smoker's Melanosis)⁶

WORKUP

Section 5 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Lab Studies

• LHS is a diagnosis of exclusion. When the diagnosis of LHS is suspected, the following tests should be performed to rule out other differential diagnoses.
• • The corticotropin level is elevated in patients with Addison disease associated with primary adrenal failure. The morning cortisol level is low, and corticotropin stimulation results are abnormal. In addition, electrolyte abnormalities, including hyperkalemia and hyponatremia, may be observed. Significant electrolyte abnormalities may be absent, and the serum potassium level is not sensitive enough to use as a screening test for Addison disease. Patients with Addison disease often report salt cravings, weight loss, and fatigue. Physical examination may reveal hypotension, pigmentation of the buccal mucosa and nails, generalized hyperpigmentation, or darkening of nevi and scars.
  • The antinuclear antibody (ANA) test is useful to screen for connective tissue diseases, including lupus erythematosus, which may cause buccal and lip hyperpigmentation. Nail streaks have not been reported in patients with lupus. Sjögren syndrome, subacute cutaneous lupus erythematosus, Coombs positive–autoimmune hemolytic anemia, and inflammatory arthritis have occurred in some patients with LHS. The significance of comorbid connective tissue disease and LHS is currently unknown.
  • Liver function test results are abnormal in hemochromatosis.

Imaging Studies

• Radiographic barium contrast studies are performed to rule out gastrointestinal polyposis in association with PJS. Most commonly, hamartomas of the jejunum are present in PJS, but they may be present anywhere throughout the gastric, intestinal, and colonic mucosae.

Other Tests

Dermatoscopic findings include the following¹⁹:

• Mucosa - Parallel patterns of pigmentation
• Nails - Longitudinal, homogeneous, regular, bandlike pigmentation with indistinct borders
• Palmar/plantar skin - Parallel, furrowed hyperpigmentation

Procedures

• Endoscopy may be performed in lieu of, or in addition to, radiographic barium contrast studies to rule out PJS.

Histologic Findings

Biopsy specimens from the oral and esophageal mucosa and from keratinized skin have been studied. Nail biopsies are rarely performed in the setting of multiple pigmented bands; therefore, nail histology has not been described.

The pigmented macules of LHS are not lentigines. They demonstrate mild-to-moderate acanthosis in most cases.³ The predominant finding is basal cell hypermelanosis. The melanin deposition in the basal layer is dense and uniform. Rete ridges may be normal in size, or they may be elongated. Numerous melanophages are often present in the papillary dermis. The basement membrane has been found to be intact. Pigment incontinence may also be present.³

Although the absence of melanocytic proliferation has been a typical pathologic feature, one study recently noted an increase of nonnested intraepidermal melanocytes in the areas of clinical hyperpigmentation using S100 and L-3,4 dihydroxyphenylalanine immunohistochemistry studies.¹

Electron microscopy reveals normal melanosome transfer to keratinocytes. Some studies suggest that melanosomes within basal keratinocytes are enlarged, whereas the melanosomes within papillary dermal melanophages are normal in size and in number.

TREATMENT

Section 6 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Medical Care

Treatment is not required, but a workup to rule out the other entities in the differential may be necessary.

Surgical Care

Q-switched Nd:YAG¹⁴ or Q-switched alexandrite^{20, 21} laser therapy may be an effective option for cosmetically bothersome melanosis on the skin. Recurrence after treatment has been reported, and sun protection is thought to be helpful in preventing recurrence.²¹ Cryosurgery has also been described, with good results.²²

FOLLOW-UP

Section 7 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Complications

• Systemic illness and malignancy are not features of LHS.

Prognosis

• LHS has a benign course. One report has described spontaneous remission.¹⁴

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

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17. Yamamoto O, Yoshinaga K, Asahi M, Murata I. A Laugier-Hunziker syndrome associated with esophageal melanocytosis. Dermatology. 1999;199(2):162-4. [Medline].
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Article Last Updated: Mar 10, 2008