Miliaria

The primary stimuli for the development of miliaria are conditions of high heat and humidity that lead to excessive sweating. Occlusion of the skin due to clothing, bandages, transdermal medication patches, ^[2] or plastic sheets (in an experimental setting) can further contribute to pooling of sweat on the skin surface and overhydration of the stratum corneum. In susceptible persons, including infants, who have relatively immature eccrine glands, overhydration of the stratum corneum is thought to be sufficient to cause transient blockage of the acrosyringium. Foxc1 knockout in mice produces miliaria, suggesting that a genetic predisposition may exist. ^[3]

If hot humid conditions persist, the individual continues to produce excessive sweat but is unable to secrete the sweat onto the skin surface because of ductal blockage. This blockage results in the leakage of sweat en route to the skin surface, either in the dermis or epidermis, with relative anhidrosis.

When the point of leakage is in the stratum corneum or just below it, as in miliaria crystallina, little accompanying inflammation is present, and the lesions are asymptomatic. In contrast, in miliaria rubra, the leakage of sweat into the subcorneal layers produces spongiotic vesicles and a chronic periductal inflammatory cell infiltrate in the papillary dermis and lower epidermis. In miliaria profunda, the escape of sweat into the papillary dermis generates a substantial periductal lymphocytic infiltrate and spongiosis of the intraepidermal duct.

Resident skin bacteria (eg, Staphylococcus epidermidis and Staphylococcus aureus) are thought to play a role in the pathogenesis of miliaria, possibly through formation of biofilms. ^[4]  Patients with miliaria have three times as many bacteria per unit area of skin as healthy control subjects do. Antimicrobial agents are effective in suppressing experimentally induced miliaria. Periodic acid-Schiff (PAS)-positive diastase-resistant material has been found in the intraductal plug that is consistent with staphylococcal extracellular polysaccharide substance (EPS). In an experimental study, only the strains of S epidermidis that produce EPS were able to induce miliaria. ^[5]

In late-stage miliaria, hyperkeratosis and parakeratosis of the acrosyringium are observed. A hyperkeratotic plug may appear to obstruct the eccrine duct, but this is believed to be a late change and not the precipitating cause of the sweat blockage.

The following causes of miliaria have been recognized:

• Immaturity of the eccrine ducts - Neonates are thought to have immature eccrine ducts that easily rupture when sweating is induced; this rupture leads to miliaria
• Occlusion of the skin, as with transdermal drug patches ^[2]
• Occlusive clothing - A case series reported 18 cases of miliaria rubra in US Army personnel who routinely wore flame-resistant army combat uniforms composed of a 65% rayon/25% Kevlar/10% nylon blend while serving in the hot, arid conditions of Afghanistan ^[6]
• Hot, humid conditions - Tropical climates, incubators in neonatal nurseries, and febrile illnesses may precipitate miliaria
• Lack of acclimatization - Miliaria is common in individuals who move from a temperate climate to a tropical climate; it usually resolves after the individual has lived in the hot, humid conditions for many months
• Exertion or high fever - Any stimulus to sweat may precipitate or exacerbate miliaria
• Type I pseudohypoaldosteronism - This disorder of mineralocorticoid resistance leads to excessive loss of salt through eccrine secretions and is associated with repeated episodes of pustular miliaria rubra (miliaria pustulosa) ^{[7, 8, 9]}
• Morvan syndrome - Miliaria rubra has been reported in this rare autoimmune disorder characterized by neuromyotonia, insomnia, hallucinations, pain, weight loss, and hyperhidrosis ^[10]
• Drugs - Bethanechol, which promotes sweating, has been reported to cause miliaria, as have clonidine and neostigmine. ^[11] ; isotretinoin, which affects follicular differentiation, has also been reported to cause miliaria as well ^[12] ; miliaria crystallina has been reported after administration of doxorubicin ^{[13, 14]}  and erythropoietin, ^[15]  as well as idarubicin with retinoic acid ^[16]
• Bacteria - Staphylococci are associated with miliaria, and antibiotics prevent miliaria in an experimental setting
• Ultraviolet (UV) radiation - Some researchers have found that miliaria crystallina preferentially occurs in UV-exposed skin ^[17]

United States and international statistics

In the United States, miliaria crystallina is a common condition that occurs in neonates (peak age, 1 wk) and in individuals who are febrile or who have recently moved to a hot, humid climate. Miliaria rubra also is common in infants and adults who move to a tropical environment; this form occurs in as many as 30% of persons exposed to such conditions. Miliaria profunda is a rarer condition that occurs in only a minority of those who have repeated bouts of miliaria rubra.

Worldwide, miliaria is most common in tropical environments, especially among people who recently moved to such environments from more temperate zones. Miliaria has been a significant problem for American and European military personnel who serve in Southeast Asia and the Pacific.

A 1986 Japanese survey that included more than 5000 neonates revealed that miliaria crystallina was present in 4.5% (mean age, 1 wk) and that miliaria rubra was present in 4% (mean age, 11-14 d). ^[18] A 2006 survey study from Iran found a 1.3% incidence of miliaria in newborns. ^[19] A survey of pediatric patients in Northeastern India reported a 1.6% incidence of miliaria. ^[20]  A hospital-based cross-sectional study of 150 patients presenting with sweat-induced dermatoses during the summer months in Puducherry, India, found that 84.1% had miliaria rubra, 4.6% had miliaria pustulosa, 3.3% had miliaria profunda, and 2.6% had miliaria crystallina. ^[21]

Age-, sex-, and race-related demographics

Miliaria crystallina and miliaria rubra can occur in persons of any age, but the diseases are most common in infants. A few cases of congenital miliaria crystallina have been reported. ^{[22, 23]}  Miliaria profunda is more common in adults than in infants and children.

No sex predilection is recognized.

Miliaria occurs in individuals of all races, though some studies have found that Asians, who produce less sweat than Whites on average, are less likely to have miliaria rubra.

Most patients with miliaria recover uneventfully within a matter of weeks, once they move to a cooler environment. The main complications that may occur are altered heat regulation and secondary infection (see Complications).

Miliaria crystallina is generally an asymptomatic self-limited condition that resolves without complications over a period of days. ^[24] It may recur if hot, humid conditions persist.

Miliaria rubra also tends to resolve spontaneously when patients are moved to a cooler environment. Unlike patients with miliaria crystallina, however, those with miliaria rubra tend to be symptomatic, often reporting itching and stinging. Anhidrosis develops in the affected sites and may last weeks. If generalized, anhidrosis can lead to hyperpyrexia and heat exhaustion. Secondary infection is another possible complication of miliaria rubra; this is manifested as either impetigo or multiple discrete abscesses known as periporitis staphylogenes.

Miliaria profunda is itself a complication of repeated episodes of miliaria rubra. The lesions of miliaria profunda are asymptomatic, but compensatory facial and axillary hyperhidrosis may develop. ^[25] The widespread inability to sweat, the result of eccrine ductal rupture, is known as tropical anhidrotic asthenia; this condition predisposes patients to heat exhaustion during exertion in warm climates.

Some authors have suggested that subclinical miliaria is an initiating step in development of atopic dermatitis, on the grounds that histopathology showed PAS-positive material and bacteria present in the acrosyringium in cases of atopic dermatitis, whereas no blockage of eccrine ducts was seen in controls. ^[26]

Patients who have had miliaria, especially miliaria profunda, must be aware of the role of heat and humidity in precipitating this condition. These patients should be advised to wear lightweight clothing, stay out of the sun, avoid exertion in hot weather, and stay in an air-conditioned environment as much as possible.