Colloid Milium

Are You Confident of the Diagnosis?

What you should be alert for in the history

Patients will describe a gradual eruption of papules or nodules on sun-exposed skin. Although usually asymptomatic, the lesions may be mildly pruritic and distressful to the patient. It is also important to ask about excess and unprotected sun exposure, petroleum exposure, hydroquinone use, and family history.

Characteristic findings on physical examination

Colloid milium is limited to the skin and tends to be distributed on sun-exposed, actinically damaged areas, particularly the cheeks, periorbital region, nose, ears, neck, dorsal hands, and forearms. Three cases of a unilateral distribution and a case of oral colloid milium have been reported as well.

Adult type: Examination will show crops of 1- to 5-mm yellow-brown or skin-colored, dome-shaped, waxy, semi-translucent, and firm papules that resemble vesicles and express mucoid or gelatinous material with pressure or puncture. The papules may easily bleed with slight trauma and form a cobblestone appearance when they coalesce (Figure 1).

Figure 1.

Nodular type: This type is similar to the adult type, but will present as a single nodule or as multiple 5- to-10 mm nodules or plaques that may be “lumpy” and telangiectatic.

Juvenile type: It is clinically indistinguishable from the adult type, but can also occur on normal skin.

Pigmented type: The color of the papules ranges from patchy gray to black. It can be associated with exogenous ochronosis.

Expected results of diagnostic studies

The diagnosis is made after examining a skin biopsy under light microscopy. Because this form of microscopy cannot distinguish colloid from amyloid, certain differentiating stains can be used. If the diagnosis is still inconclusive, electron microscopy may be helpful.

Histologic examination will show fissured homogenous glassy eosinophilic colloid masses deposited in the dermis, with occasional capillary dilation and sparing of the hair follicle and sebaceous gland. There is no inflammation, but a few lymphocytes and mast cells may be present. Colloid milium is positive for periodic acid-Schiff stain and can show green birefringence with Congo Red stain. It is generally negative for methyl (crystal) violet, cytokeratin, and immunoglobulin light chain stains.

Adult type: Islands of colloid material will be in the papillary dermis with extension into the mid dermis. Fracturing clefts split these deposits into smaller islands and have intervening stellate and spindle-shaped fibroblasts. A narrow grenz zone, which spares the subepidermal layer of the papillary dermis from colloid deposition, also exists. Solar elastosis is often present immediately adjacent to colloid deposits.

Nodular type: Deposits are similar to the adult type, but exist in most of the dermis. The epidermis may be atrophic and basal keratinocytes may appear hyalinized due to degeneration.

Pigmented type: Deposits are similar to that of the adult type, but appear light golden, as is characteristic of ochronosis.

Juvenile type: Fissuring colloid masses are seen close to the basal layer of the epidermis and may transition into the dermis. The substance seems to originate from degenerating epidermal keratinocytes and contains damaged organelles and desmosomes. Initially, the deposits have degenerating and clumping tonofilaments that later transform into whorls and wavy bundles. Basement membrane damage is sometimes present. Unlike the other types, there is no grenz zone or solar elastosis, and it is typically negative for Congo Red and positive for antikeratin antibody.

Under the electron microscope, colloid material appears as short, wavy, and branching electron-dense filaments that are 1.5 to 2 nm in diameter, and may show transitional stages between actinic elastoid and colloid.

Diagnosis confirmation

The differential diagnosis may include systemic amyloidosis, primary cutaneous amyloidosis, basal cell carcinoma, epidermal inclusion cyst, erythropoietic protoporphyria, lipoid proteinosis, molluscum contagiosum, sarcoidosis, sebaceous hyperplasia, steatocystoma multiplex, syringoma, trichoepithelioma, papular mucinosis, and tuberous sclerosus. A careful history and interpretation of the skin biopsy can distinguish colloid milium from all these conditions.

Amyloidosis is the most difficult to rule out clinically and histopathologically. The deposits in colloid milium tend to be larger and have coexisting solar elastosis and epidermal atrophy, whereas amyloidosis is associated with hyperplasia. Immunohistochemically, both colloid and amyloid are periodic acid-Schiff positive and colloid, like amyloid, can show green birefringence with Congo Red. Usually, only amyloid is positive for methyl (crystal) violet, cytokeratin, and immunoglobulin light chain stains.

Under the electron microscope, colloid material appears as short, wavy, and branching electron-dense filaments that are 1.5 to 2 nm in diameter, and may show transitional stages between actinic elastoid and colloid. In contrast, amyloid material appears as straight filaments that are 6 to 10 nm in diameter.

Who is at Risk for Developing this Disease?

Colloid milium is a rare condition of unknown incidence and prevalence. About 100 cases have been reported, with the consensus being that many more exist. Colloid milium can be classified into four types: adult, nodular (or paracolloid), pigmented, and juvenile. The adult form is the most common and is usually seen in middle-aged fair-skinned males. Risk factors include unprotected light exposure (particularly ultraviolet [UV] A), fair complexion, outdoor occupations, and exposure to petroleum derivatives, such as phenols.

Risk factors for the nodular type are less established, but may include sun exposure. The pigmented form seems to occur with chronic use of hydroquinone cream combined with excess sun exposure. The juvenile form develops before puberty and the risk depends on family history.

What is the Cause of the Disease?

Etiology

Possible risk factors have been identified, but the origin and mechanism of pathogenesis remain unclear. For the adult and nodular forms, unprotected and prolonged UV exposure is likely responsible for the skin degeneration. The development of the adult type on the dorsal hands of 28 oil refinery workers in the tropics and a mechanic, who were all exposed to lubricating oils and sun, suggests an interaction between light and petroleum products.

The pigmented form is associated with chronic use of hydroquinone bleaching cream and sun exposure, probably because phenols present in the cream increase sensitivity to UV damage. Patients with juvenile colloid milium likely have an inherited susceptibility to UV light that can be transmitted autosomal recessively.

Pathophysiology

The most established theory argues that the colloid deposits are secondary to elastic fiber degeneration. Immunohistochemical evidence includes the presence of microfibrillar proteins like serum amyloid P, sulfur-containing amino acids, and various microfibril-specific sugar residues. The absence of hydroxyproline and hydroxylysine rules out a collagen source.

UV light may either directly damage the elastin or indirectly affect its synthesis by damaging fibroblasts. Additionally, UV exposure may activate elastinolytic enzymes, such as elastase and protease. The juvenile type may be secondary to UV-induced keratinocyte damage.

Systemic Implications and Complications

Colloid milium is limited to the skin. No complications or fatalities have been reported.

Treatment Options

No satisfactory therapies are currently available. Treatment options are summarized in the Table 1.

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