Laugier-Hunziker Syndrome

Background

Laugier-Hunziker syndrome (LHS) was initially described in 1970 as acquired, benign hyperpigmented 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 Laugier-Hunziker syndrome, 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]

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Pathophysiology

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

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Etiology

The etiology of melanosis in Laugier-Hunziker syndrome is unknown.

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Epidemiology

Frequency

United States

The incidence is rare, but it is likely underreported. White patients and those of Latino descent 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]

Race

Laugier-Hunziker syndrome mainly affects whites; however, persons of Hispanic, Arabic, or Asian^[5] 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 Laugier-Hunziker syndrome 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

Laugier-Hunziker syndrome was initially predominantly thought to affect females, with an estimated female-to-male ratio of 2:1.^[6] However, the idea that Laugier-Hunziker syndrome 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 years^[7] and a median age of 42 years^[8] 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 Laugier-Hunziker syndrome, 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.

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Prognosis

Laugier-Hunziker syndrome has a benign course. One report has described spontaneous remission.^[9]  Systemic illness and malignancy are not features of Laugier-Hunziker syndrome. Such findings in association with mucocutaneous melanotic hyperpigmentation exclude the diagnosis of Laugier-Hunziker syndrome.

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Physical Examination

Oral pigmentation^{[6, 10, 11, 12]} 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. The latter three may also help distinguish Laugier-Hunziker from Petz-Jeghers syndrome.^[13] 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. Cutaneous lesions may fade following puberty; however, oral hyperpigmentation occurs gradually and is considered permanent. Of the five cases originally described by Laugier and Hunziker, 40% had oral involvement only. Subsequent reports have also described the onset of oral pigmentation following melanonychia. Melanoacanthomas have also been reported.

See the image below.

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Oral findings in Laugier-Hunziker syndrome. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/colour/laugier1.jpg).

Nail hyperpigmentation^{[6, 14, 15, 16]} 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 four 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 (melanonychia)

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 Laugier-Hunziker syndrome,^{[9, 17]} sometimes on various nails of the same patient. Pigment may also involve the lateral nail folds.

See the image below.

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Nail findings in Laugier-Hunziker syndrome. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/colour/laugier2.jpg).

Extended mucocutaneous pigmentation has become a recognized feature of Laugier-Hunziker syndrome.^[18] 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 Laugier-Hunziker syndrome. Patients with Laugier-Hunziker syndrome involving the conjunctiva, sclera, and esophageal mucosa have also been reported.^{[1, 3, 19]}

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Complications

Systemic illness and malignancy are not features of Laugier-Hunziker syndrome (LHS). Thrombocytopenia and anemia have been reported in association with Laugier-Hunziker syndrome; however, systemic illness is not typically seen.^[20]

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Laboratory Studies

Laugier-Hunziker syndrome (LHS) is a diagnosis of exclusion. When the diagnosis of Laugier-Hunziker syndrome is suspected, 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 Laugier-Hunziker syndrome. The significance of comorbid connective tissue disease and Laugier-Hunziker syndrome is currently unknown.

STK11 gene testing may be performed to evaluate for Peutz-Jeghers syndrome.^{[22, 23]}

Liver function test results are abnormal in hemochromatosis.

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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.

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Other Tests

Dermatoscopic findings have been reported and include the following^{[24, 25]} :

• Mucosa - Parallel patterns of pigmentation
• Nails - Longitudinal, homogeneous, regular, bandlike pigmentation with indistinct borders
• Palmar/plantar skin - Parallel, furrowed hyperpigmentation
• Vulva - Parallel pattern with partially linear and partially curvilinear, light to dark brown streaks
• Lips - Linear streak like brown pigmentation caused by skin furrows and reliefs associated with multiple brown dots of different sizes distributed regularly throughout the lesion^[24]

Dermatoscopic findings vary widely given the different locations involved. Further evaluation of these findings is needed to better establish dermatoscopic criteria for this condition.

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Procedures

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

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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 Laugier-Hunziker syndrome 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, recent studies recently noted an increase of nonnested intraepidermal melanocytes in the areas of clinical hyperpigmentation using S100 and L-3,4 dihydroxyphenylalanine immunohistochemistry studies.^{[1, 7]}

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Medical Care

Laugier-Hunziker syndrome (LHS) does not require treatment, but a workup to rule out the other entities in the differential may be necessary.

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Surgical Care

Q-switched Nd:YAG^[9] or Q-switched alexandrite^{[22, 23, 26, 27, 28]} 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.^[27] Cryosurgery has also been described, with good results.^[29]

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Long-Term Monitoring

No long-term monitoring is needed, as there are no associated complications with Laugier-Hunziker syndrome. It is important to make the diagnosis and differentiate it from other conditions like Peutz-Jeghers syndrome that require more aggressive long-term monitoring.^[22]

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