Introduction

Milia are small cysts that form when a protein called keratin becomes trapped under the outer layer of the skin. Milia have a characteristic appearance - either appearing as firm and pearly white, or yellow, bumps. They are commonly found on the eyelids, forehead, cheeks, and even the genitalia area, and can manifest as individual cysts or in groups. In most cases, clinical treatment is not recommended or necessary, as milia are harmless and typically self-resolve. However, as an affected patient, it is helpful to understand how milia develops (and the risk factors affecting milia development) to distinguish it from other skin conditions.¹

Causes of milia

Primary milia

Primary milia are the direct result of keratin becoming entrapped in the skin, typically on or close to the lower sebaceous glands area of hair follicles. Primary milia are more common than secondary (or acquired) milia, which will be discussed later.² 

Congenital neonatal milia

Neonatal milia are a type of primary milia seen in ~50% of newborns. They are commonly referred to as primary congenital milia.² These milia are typically asymptomatic, appearing at birth and disappearing spontaneously within the first few months of life. The exact cause of developing neonatal milia is unknown. 

This type of milia usually presents on the face as tiny white bumps and, although they are similar to baby acne, they are smaller and present at birth.³ Over time, these blocked-off skin pores will open up without treatment. Neonates may also have milia present on the palate (known as Epstein pearls) or even on the gums (known as Bohn nodules). Luckily, like facial milia, these cysts will self-resolve.⁴ Another larger type of variant of neonatal milia, epidermal inclusion cysts, may be present on the penis or scrotum. Again, these will self-resolve without treatment.⁴

Benign primary child and adult milia 

Milia can also appear in children and adults and often develop spontaneously. Similarly to neonatal milia, primary milia in adults and children can be found on the face and genitalia, with a common area being along the nasal crease.²

Milia en plaque

Milia en plaque is a type of milia that is seen in children and adults, with middle-aged women being commonly affected. They can be described as multiple milia with erythematous plaques around several centimetres in size. They are found on the jaw, cheek, eyelid, or behind the ear. 

Milia en plaque is associated with several genetic and autoimmune conditions, including lichen planus, pseudoxanthoma elasticum, and discoid lupus erythematosus.²

Multiple eruptive milia

Multiple eruptive milia is another type of milia that often appears over weeks or months.¹ They can be asymptomatic or itchy and are found on the face, upper arms, and body. The cause of these milia can be sporadic (unknown and random), or they can be inherited from a parent.⁵

Nevus depigmentosus with milia

Nevus depigmentosus is a congenital skin disorder causing patches of skin to become hypopigmented (lighter than the surrounding skin). It not only affects the skin's production of melanocytes (pigment-producing cells), but it also alters the normal functions of the skin - creating an environment where keratin is more likely to become entrapped and produce milia.⁶

Genetic causes of primary milia 

There are also several associated genetic conditions (genodermatoses) with primary milia which include:^7,8

• Gardner Syndrome
• Rombo syndrome
• Basal cell naevus syndrome
• Bazex-Dupre-Christol syndrome
• Pachyonychia Congenita
• Oro-facial digital syndrome type 1
• Congenital hereditary trichodysplasia

These genodermatoses can make individuals more likely to develop milia, as they can affect the body’s ability to shed skin and disrupt keratinisation.¹

Secondary milia

Unlike primary milia, secondary milia are commonly caused by entrapped keratin at sweat glands (eccrine ducts). They commonly affect older children and adults. The development of secondary milia can be triggered by trauma, medication, or other underlying diseases. As secondary milia do not always self-resolve, treatment may be required - including surgical methods, topical retinoids or, even chemical peels.¹ 

Trauma-associated milia 

Secondary milia may be caused as a result of skin injuries, burns or abrasions. For example, individual or multiple milia can form on injured sweat glands as they begin to heal.⁹

Trauma-associated milia are often seen in/after:^10,11,12

• Burns
• Sunburns 
• Surgical procedures like dermabrasion, skin grafting and laser resurfacing
• Chemical peels - milia appear in the first few weeks of recovery. The ointments given to patients after a peel can block hair follicles, increasing the risk of milia forming. 
• Tattoos
• Photodynamic therapy - milia is a rare side effect brought on by damage to the dermal-epidermal junction 
• Radiotherapy
• Heel stick procedure - this procedure is used to collect blood samples from young babies and can cause milia at the skin prick site

Medication-associated milia 

Secondary milia can also occur as an adverse effect of some medications, such as: 

• Topical steroids e.g. hydroquinone or 5-fluorouracil cream
• Nitrogen mustard ointment
• Corticosteroids e.g. clobetasol propionate cream 
• Cancer drugs e.g. vemurafenib and dovitinib
• Nonsteroidal anti-inflammatory drugs (NSAIDs)

These medications can cause skin thinning and affect skin regeneration, increasing the risk of milia forming. Alternative treatments can often be offered if you experience milia as a side effect of any prescribed medication.¹³

Disease-associated milia

Blistering diseases

Blistering diseases include conditions like epidermolysis bullosa, epidermolysis bullosa acquisita, bullous pemphigoid, and lichen planus. Groups of milia often appear in areas of previous blistering. Porphyria cutanea tarda is also another blistering disease associated with milia forming on the backs of the hands and fingers.² 

It is unknown exactly why milia appear in these cases, but it has been suggested that the immune system’s reaction to blistering diseases, and the abnormal interactions between types of skin cells and layers during blistering, could be responsible.¹⁴ 

Risk factors for milia 

Risk factors that increase the chance of milia developing include:¹⁵

• Age: although milia can occur in all age populations, neonates and older adults are at increased risk. 
• Skin damage: patients with long-term skin damage through sun exposure, injury/trauma or blistering skin diseases are at an increased risk of milia.
• Long-term use of medications associated with milia development, like topical steroids. 
• Lifestyle factors: lack of proper skin care, use of oil-based products on the skin, or lack of sleep can all affect the skin and create an increased risk of trapped keratin cysts.

Summary 

Milia are small white-yellow cysts that form on the eyelids, forehead, cheeks, and area around the genitals. They form when keratin (a skin protein) becomes trapped under the outer layer of the skin.¹ There are two classifications of milia: primary milia, which are caused directly by entrapped keratin, and secondary milia, which are caused by keratin becoming trapped at sweat glands due to skin injury, disease, or medication.² 

Primary milia are often seen in neonates, but they can also appear spontaneously in older populations. They are occasionally associated with genetic diseases and can be further classified into variants such as milia en plaque, multiple eruptive milia, and nevus depigmentosus with milia.¹ Secondary milia can be caused by trauma, medication or other underlying diseases.⁹ There are several risk factors that can increase the likelihood of developing milia, including age, previous skin damage, long-term use of medications associated with milia, lack of proper skincare, and poor sleep.⁵ Whilst this skin condition is generally self-limiting (meaning it goes away without treatment), patients should be aware of the underlying causes of milia in case they need to seek further medical attention.¹