Ocular Mycobacterium haemophilum infection originating in the ... - BMC Infectious Diseases

Most infections caused by M. haemophilus occur in immunocompromised populations (e.g., HIV-infected patients, organ transplant recipients, patients with autoimmune diseases, and those with IgA deficiency), patients with uncontrolled diabetes, and young children [8,9,10,11]. Immunocompetent individuals are rarely infected by M. haemophilus. However, in recent years, patients have been reported to be infected by tattoos, eyebrow tattooing, and acupuncture [12, 13], and trauma can lead to M. hemophilus infection. In addition, multiple ocular surgeries may cause ocular M. haemophilus infections [14].

The patient reported herein was a healthy adult with no medical history. All systemic examinations performed after eye infection were normal, and no infections were found in other parts of the body. The patient, a gold miner who had worked in a wet environment for a long time, may have been exposed to sewage containing M. haemophilus. Unnoticed or undetected trauma, such as the casual eye injury, may have likely transmitted the bacteria and cause his illness. This case differs from other reported ocular infections, because the infection was initially located in the cornea. After therapeutic keratoplasty, we thought that the lesions had been removed and the infection had been cured; however, the conjunctival infection had been arised by local spread. The conjunctival infection was speculated to have originated from the direct spread of bacteria, and the eyelid infection was due to continuous or lymphatic dissemination. In addition, local use of corticosteroids may also accelerate the spread of infection. Pisitpayat et al. [8] reported a case of scleritis and keratitis caused by M. haemophilus in a healthy adult, similar to our case. However, the case reported by Pisitpayat et al. may have been an initial sclera-infection. Therefore, our case is the first reported corneal-initial M. haemophilus infection that showed no evidence of any systemic association.

The lack of specific signs and the very slow onset of keratitis caused by M. haemophilus, together with the specific culture requirements of this mycobacterium, makes the diagnosis of this disease very difficult. This slow-growing mycobacterium usually requires eight weeks to grow in media at 30–32 °C, which is lower than the temperature required by other NTMs (35–37 °C). In addition, it requires the addition of hemin or a high-valent iron complex in the media, hence the name "Haemophilus" [6]. Inappropriate culture techniques may lead to false negative results. Ziehl-Neelsen staining of corneal scrapings and tissue specimens is a diagnostic method for mycobacterial infection. However, we did not consider a rare infection, such as mycobacteria, in our patient, and consequently did not adopt this test. High-throughput DNA sequencing was used to confirm the diagnosis. PCR detection is also a reliable and widely used method for the rapid diagnosis of pathogens.

The ophthalmologist had no experience with the clinical features of M. hemophilus keratitis. The patients with keratitis reported by Pisitpayat et al. [8] initially presented with radial keratitis, which was misdiagnosed as viral keratitis, and were administered antiviral therapy and long-term glucocorticoid therapy. This approach can control symptoms; however, the condition worsens dramatically. Similarly, the patient described herein was initially misdiagnosed with HSK at a local hospital and was misdiagnosed with HSK after visiting our hospital because the corneal lesions showed geographic epithelial defects and infiltration. After antiviral and glucocorticoid therapy, the patient's inflammatory response was alleviated, but the range of the lesions gradually expanded. A study by Ford et al. [3] found that 80% of patients with NTM keratitis who received topical glucocorticoids did not respond to antibiotics. Glucocorticoid therapy reduces local host immune defenses and contributes to the development and progression of NTM keratitis.

Histopathologically, the most commonly reported cutaneous manifestations of M. haemophilus infection are mixed granulomas and a purulent reaction with various histological changes, including panniculitis, ulcer necrosis, abscess formation, lichenoid interface dermatitis, and lymphocyte vasculitis [15]. The patient described herein presented with caseous necrosis in the conjunctival lesions, and histopathological examination also showed granulomatous findings. Therefore, mycobacterial infections should be suspected when similar findings are observed.

A consensus on the treatment modality and duration of M. haemophilus infection is currently lacking. Moxifloxacin, clarithromycin, azithromycin, rifampicin, levofloxacin, and amikacin are commonly used antibiotics reported in the literature, and three to four types of antibiotics should be systemically used in combination to adequately control infection. Nookeu et al. [16] believed that the treatment of M. haemophilus infection should last for 3–12 months and should be tailored to the severity of the disease and immunocompromised conditions. Recurrence cases have also been reported. Lindeboom et al. [7] reported a recurrence rate of 4% in cases of M. hemophilus infection, whereas Nookeu et al. [16] reported a recurrence rate of 14%. Therefore, the patient's status should be carefully monitored after treatment discontinuation. Prompt surgical resection of the lesion is considered an effective treatment method. For patients with severe corneal infections, therapeutic keratoplasty can be considered; however, if the corneal lesions are not completely removed, the risk of recurrence is high. Infections in the peripheral cornea can progress to the limbus, leading to infections of the conjunctiva, sclera, and even endophthalmitis. Conjunctival and skin infections can be treated with debridement.

In conclusion, M. haemophilus could cause primary infection of the cornea in healthy adults and spread to other tissues of the eye by direct and hematogenous spread. High-throughput DNA sequencing can quickly provide an accurate diagnosis. Therapeutic keratoplasty and debridement of necrotic tissue are effective treatments for severe infection. Long-term and systemic administration of sensitive antibiotics is a necessary strategy for a radical cure. The patient's status should be monitored on a long-term basis for the timely detection of recurrent infections. Once diagnosed, glucocorticoid use should be stopped to avoid the spread of infection.