Mycobacterium marinum

Swimming pool granuloma, aquarium granuloma, fish tank granuloma, swimming pool granuloma. Mycobacterium balnei is now M. marinum.

Mycobacterium marinum is a non-tuberculous mycobacterium (NTM) that occurs worldwide in water. It grows slowly, is photochromogenic and prefers to infect skin and subcutaneous tissue after inoculation through skin lesions in water (e.g. aquariums). As it grows optimally at approx. 30 °C and hardly proliferates at core body temperature (37 °C), the infection usually manifests itself on cooler, superficial areas of the body (extremities) as chronic granulomatous skin lesions. Systemic courses are rare. If left untreated, the infection can persist and become chronic and progressive.

Cutaneous infections caused by M. marinum are rare, sporadically occurring mycobacterioses worldwide. The risk exists primarily in people with regular contact to contaminated fresh or salt water, such as aquarium owners, fish farmers, fishermen or through bathing in insufficiently disinfected waters and fish pedicures. Tropical climates and travel increase the risk of exposure. Immunosuppression aggravates the course and can lead to disseminated infections, but does not increase the primary risk of infection. M. marinum is one of the most common non-tuberculous mycobacteria in cutaneous infections.

Cutaneous M. marinum infections are classified clinically according to spread and depth of infestation:

1.  Localized cutaneous form: Single skin lesion (granuloma) at the site of inoculation without dissemination. This is the most common manifestation in immunocompetent patients.
2. Lymphocutaneous form (sporotrichoid): Successive development of multiple secondary nodules or ulcers along the regional lymphatics. This pattern is observed in about 20-40% of cases of marinum disease.
3. Deep form (soft tissue and bone involvement): The infection can spread to deeper structures if the course is prolonged or treatment is inadequate. Typically, tendon sheaths (tenosynovitis), bursae (bursitis) or joints (septic arthritis) are affected, particularly in the hand. Osteomyelitis of adjacent bones is less common.
4. Disseminated (systemic) form: Extremely rarely, M. marinum spreads systemically and causes multiple lesions. This occurs almost exclusively in severely immunosuppressed patients.

Transitions between the forms are possible. Sporotrichoid and deeper courses are considered more complicated special forms, while the disseminated form is very rare.

Mycobacterium marinum is an environmental germ that occurs naturally in bodies of water, aquaria and on fish. Transmission to humans occurs through penetration via skin injuries or microtraumas on contact with the contaminated environment (e.g. through fish spines or when handling aquaria). M. marinum prefers cool temperatures and multiplies optimally at ~30 °C. After penetration into the skin, a granulomatous inflammation with the formation of granulomas becomes established. The bacterial load is often low. The pathogen has virulence factors that promote survival in macrophages. There is virtually no human-to-human transmission - the infection remains confined to the site of exposure, except in the rare case of dissemination in immunodeficiency. The incubation period is typically 2-4 weeks, but can also be several months.

Chronic skin lesions in the area of the inoculation site are in the foreground. Initially, a small erythematous-livid papulonodule usually appears, which slowly increases in size. The lesion may appear verrucous (wart-like) or ulcerate and develop a crusty surface. It is often only slightly painful or sensitive to pressure and has an indolent course. If left untreated, the granuloma persists for weeks to months.

In the sporotrichoid form, further rough, reddish lumps or abscesses develop one after the other along the associated lymphatic channels, often on the extensor side of the extremity proximal to the primary lesion. These secondary lesions can ulcerate and secrete secretions. Swelling and restricted movement may occur in surrounding joints or tendon sheaths if the lesion is deep.

Accompanying systemic signs of inflammation are usually mild. Occasionally, regional lymphadenopathies or signs of lymphangitic dissemination (reddish streaks) are found in the vicinity of the lesion. Fever and clear signs of illness are atypical. Overall, the skin symptoms are similar to those of other granulomatous infections, which can make clinical differentiation difficult.

The diagnosis is made on the basis of the patient's medical history, clinical findings and laboratory confirmation. The typical exposure (aquarium, fish contact) in combination with a slowly progressive, therapy-resistant skin granuloma can be a clue. Suspected cases should be specifically clarified, as standard tests (routine bacterial cultures, direct fungal detection) often remain negative.

Histopathology: The skin biopsy shows granulomatous inflammation with epithelioid cell granulomas and possibly central necrosis. In early stages, neutrophilic microabscesses ("suppurative granulomas") are also found. Special stains (Ziehl-Neelsen, Fite stain) can detect acid-fast rods, but direct pathogen detection in histologies is only successful in around 20-50 % of cases (paucibacillary nature of the infection).

Microbiological pathogen detection: The gold standard is the culture of the pathogen from biopsies or pus. M. marinum grows on special mycobacterial media (Löwenstein-Jensen, Middlebrook agar) within 1-3 weeks at 28-32 °C. It is important to inform the laboratory of the suspicion so that the cultures can be incubated at the appropriate temperature. In culture, M. marinum shows rough, yellowish pigment formation (photochromogenesis) after exposure to light. In parallel or alternatively, PCR with gene sequencing (e.g. 16S rRNA gene) enables rapid identification from tissue samples. MALDI-TOF mass spectrometry can also be used in specialized laboratories for species identification.

Further tests: Serological or immunological tests are non-specific. Interferon-γ release assays (IGRA) that react to M. tuberculosis usually remain negative, as M. marinum does not induce ESAT-6/CFP-10 secretion in humans. However, cross-reactions have been described, so that a positive IGRA does not reliably differentiate between tuberculosis and M. marinum infection. A positive tuberculin skin test (PPD) can occur in atypical mycobacterioses, but is also not specific.

The diagnosis is confirmed when M. marinum is cultured from the lesion or identified by nucleic acid detection. Clinicopathological constellation (exposure, chronic floating granuloma, granulomatous histology, exclusion of M. tuberculosis and sporotrichosis) can support the diagnosis in individual cases, but must be confirmed by microbiological pathogen detection.

Typically, M. marinum infections manifest on the upper extremities, often on the hands and fingers as well as the forearm or elbow. This correlates with injuries from contact with contaminated water or fish. Lesions can also occur on the lower extremities, for example on the knees, shins or feet after contact with water or fish pedicures. The preferred localization on cooler parts of the body is explained by the growth optimum of M. marinum at lower temperatures; warm regions are primarily rarely affected. In the case of chronic skin nodules, particularly on the hands or knees, contact with water or fish should be investigated.

There is often a history of injury due to contact with an aquatic environment a few weeks before the skin lesion occurs. Both obvious and smaller, unnoticed skin lesions can serve as entry points. A latency of several weeks between exposure and onset of symptoms is typical and should indicate a possible atypical infection. It is crucial to ask specifically about aquatic exposure, as patients often do not make this connection. Often another diagnosis is initially made and treated without success. In immunocompromised patients, a history of relevant foreign travel or aquarium ownership should be obtained, as multiple lesions or unusual progressions may occur.

Histologically, the skin biopsy of a M. marinum infection shows epithelioid cell granulomas with variable caseous necrosis, similar to lupus vulgaris. Suppurative components such as neutrophilic microabscesses are also frequently found within the granulomas, which may be reminiscent of pyogenic infections or sporotrichosis. The epidermis often shows pseudoepitheliomatous hyperplasia. In advanced lesions, abscesses and fistulous tracts may form.

Ziehl-Neelsen staining for acid-fast rods is positive in about half of the cases, but direct detection in tissue is not always successful due to low pathogen density. Histologically, M. marinum cannot be distinguished from other atypical mycobacteria or sporotrichosis; culture or PCR are therefore essential for definitive detection. In immunocompromised patients, granuloma formation may be less pronounced or absent. Dermatopathology confirms the granulomatous character and helps with differential diagnoses; the exact etiology requires laboratory diagnostics.

Untreated M. marinum infections can spread and cause functional impairment. Complications include spread to deeper hand structures such as tendons or joints, causing swelling, pain and restricted movement, which can lead to tissue destruction and permanent functional impairment if left untreated. In the case of immunodeficiencies, there is a risk of hematogenous spread with multiple skin lesions or infestation of internal organs. Misdiagnosis and inappropriate therapies, such as steroids, can promote the spread of the disease. Secondary infections or scarring are further possible complications. Although the prognosis of localized infections is good with adequate treatment and usually only scars remain, early diagnosis and consistent treatment are crucial to avoid serious complications and permanent damage.

The prognosis of M. marinum skin infections is good with timely and adequate antibiotic treatment. The lesions usually heal over a period of months, often with residual scars that are functionally irrelevant. Early diagnosis is crucial; it prevents chronic progression and complications such as joint involvement. In immunosuppressed patients, the prognosis is more cautious, with a risk of protracted or disseminated courses and relapses. Reinfections are rare. The prognosis depends heavily on the patient's immune status and the pattern of infection: Immunocompetent patients with localized infestation usually heal completely; severely immunocompromised patients have a higher risk of therapy-resistant courses. Close follow-up care is advisable until complete healing.

As M. marinum enters opportunistically via injuries, prevention is crucial. When handling potentially contaminated water (aquariums, ponds, fish), waterproof protective gloves and suitable clothing are important, especially for wounds. Thoroughly clean and disinfect injuries in this environment immediately. Public swimming pools require adequate chlorination. Immunocompromised people should avoid aquariums and fish spas. Exercise caution during freshwater activities in tropical regions and treat injuries immediately. Disinfect any skin injury after contact with natural or aquarium water. Prophylactic antibiotics or a vaccine do not exist; consistent hygiene and protective clothing are the best protection.

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