Excerpt from Nocardiosis

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Background

Nocardiosis is an infection caused by several species of soil-borne aerobic bacteria belonging to the genus Nocardia. Similar to anaerobic organisms of the genus Actinomyces, Nocardia species often form thin filaments that can resemble but are much thinner than those of true fungi (1-2 µm vs 3-5 µm in diameter).

Nocardiosis can be divided into 2 broad categories, disseminated and cutaneous.

Disseminated nocardiosis

Disseminated nocardiosis is responsible for most occurrences of nocardiosis, is most commonly caused by Nocardia asteroides, and typically affects immunocompromised hosts, although individuals with presumed immunocompetency also can develop the disease.

Primary cutaneous nocardiosis

Primary cutaneous nocardiosis, most commonly caused by Nocardia brasiliensis, typically affects immunocompetent individuals with a history of trauma and can be subdivided into 3 clinical entities that include (1) lymphocutaneous infection, (2) mycetoma, and (3) superficial skin infection, including ulceration, abscess, and cellulitis. Involvement of the skin can occur as a result of secondary dissemination from systemic infection. Cutaneous involvement with N asteroides is usually secondary to hematogenous dissemination from a pulmonary focus. Dissemination to the skin is estimated to occur in approximately 10% of patients with systemic nocardial infection, second in incidence only to CNS involvement.

Lymphocutaneous nocardiosis

Lymphocutaneous nocardiosis is rare and often misdiagnosed as sporotrichosis (more common) because it also manifests as a primary lesion at the site of injury, followed by a proximal spread of lymphangitis and nodular lesions along the lymphatics. The lymphocutaneous or sporotrichoid form is the least common form of primary cutaneous nocardiosis. However, it probably is more common than reported, and diagnosis requires a high index of suspicion. Of 14 patients reported from 1920-1986, more than half had a history of gardening or thorn injuries.

Mycetoma

Mycetoma, also termed maduromycosis or Madura foot, is named after the Indian region where it was first described. Mycetoma is a chronic, deep, progressively destructive, and deforming infection of skin, subcutaneous tissues, fascia, bone, and muscle following localized trauma. The disorder occurs most commonly on the extremities, especially the foot. Mycetoma manifests as a tumorlike area of localized edema or massive enlargement, with erythema and multiple draining sinus tracts. Often, mycetoma is described as a triad of tumefaction, sinus tract formation, and grains (sulfur granules).

Approximately half the mycetoma occurrences are caused by Nocardia species. In Mexico and Central and South America, N brasiliensis is the agent involved in 90% of mycetomas.

Mycetoma caused by filamentous bacteria is termed actinomycetoma. Actinomycetoma can be caused by N brasiliensis, N asteroides, Nocardia madurae, Streptomyces somaliensis, Streptomyces pelletieri, and Actinomyces israelii.

Mycetoma caused by true fungi is termed eumycetoma. Eumycetoma can be caused by Pseudallescheria boydii, Phialophora jeanselmei, Madurella mycetomi, Madurella grisea, Cephalosporium falciforme, and Cephalosporium recifei.

In the United States, mycetoma is rare and is more commonly caused by P boydii than nocardial or other organisms. Histologically, mycetoma is often granulomatous and fibrosing and is the only clinical form of nocardiosis regularly associated with sulfur granules.

Superficial skin infection

The remaining primary skin infections of nocardiosis manifest as pustules, abscesses, or cellulitis and often mimic disease caused by more common organisms, such as Staphylococcus species. Nocardiosis probably causes superficial skin infections much more commonly than reported. The reason for this is 2-fold. First, most of these infections are treated empirically, and cultures often are not performed. If the infection clears, it is assumed it to have been of staphylococcal or streptococcal origin. Second, Nocardia is a slow-growing bacterium that rarely appears in culture prior to 48 hours. If no growth is seen within 48 hours, cultures are often discarded, and no definitive diagnosis is made.

One case report of infectious neutrophilic eccrine hidradenitis has been attributed to nocardiosis. Neutrophilic eccrine hidradenitis is more commonly seen with the use of chemotherapeutic agents.

Pathophysiology

Virulent strains of Nocardia species are often facultative intracellular pathogens that successfully evade the host's immune response by resisting phagocytosis, inhibiting phagosome-lysosome fusion, and resisting the oxidative killing mechanism of phagocytes. Cell-mediated immunity, triggered by activated macrophages and the induction of lymphocyte-mediated killing of Nocardia organisms, is the body's primary defense against these pathogens.

Pulmonary disease is the most common manifestation of nocardial infection. Dissemination has been found in almost every organ, most commonly in the brain and skin. Nocardiosis commonly results in multisystemic illness, particularly in immunocompromised patients.

Frequency

United States

According to the Infectious Disease Society of America, 500-1000 patients with nocardiosis present annually. Many sources report that skin is primarily involved in 5-7% of these infections. Most experts believe this figure is underestimated because many nocardiosis infections mimic more common diseases and are treated with drainage and antibiotics, without identification of the causative organism. Superficial skin infection, including abscess and cellulitis, is the most common subtype of nocardiosis in the United States. Currently, mycetoma is relatively rare in the United States. Most patients with clinical cases caused by N brasiliensis have been seen in the south and southwestern United States.

International

Rates of nocardiosis vary by country. For example, in Japan, 45 patients with cutaneous nocardiosis were reported by 1985. Approximately 90% of those patients had mycetoma. Worldwide, mycetoma is the most common cutaneous manifestation of N brasiliensis infection and is described most often in Mexican and South American field workers.

Mortality/Morbidity

Most cutaneous nocardiosis infections resolve without significant mortality; however, secondary hematogenous dissemination with subsequent mortality has been reported. Morbidity is most significant with the chronic mycetomal form, which may persist for years and may be incurable. The lymphocutaneous type usually responds well to antibiotic therapy within 2-3 months, and superficial skin infections often resolve with empiric antibiotics.

Race

Nocardiosis is primarily related to geographic distribution rather than ethnicity and is more common in Mexican and South American populations.

Sex

The male-to-female ratio is 3:1 in all forms of nocardiosis. The predominance of men performing outdoor labor, rather than an inherent predisposition, may be responsible for this ratio. The lymphocutaneous or sporotrichoid form has a greater than 80% male predominance.

Age

Primary cutaneous nocardiosis may occur in persons from any age group but is more common in middle-aged adults, especially men. Cervicofacial nocardiosis is a subgroup of the lymphocutaneous type that affects children and is clinically distinguishable because it occurs in children, manifesting as facial pustules or papules with associated cervical or submandibular lymphadenopathy and fever without a history of trauma.

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