Disseminated nocardiosis is defined as two or more noncontiguous sites of involvement, including pulmonary focus or not. The infection in our patient involved multiple systemic organs and nocardia bacteria was found by the culture of puncture fluid, based on which the diagnosis of disseminated nocardiosis was established. After receiving combination antibiotic treatment, the patient almost completely recovered from the disease.
The clinical manifestations of nocardia infections are very heterogeneous and nonspecific. Lung, brain and skin are the most common affected sites[6]. Lung is the primary site for nocardia infection in more than 70% patients. Brain infection is found in approximately 20% cases. The infection also involved skin, muscle, heart, and kidney. Our patient had the lesions in these common sites, including lung, brain, and skin. Furthermore, ocular tissue of our patient was also involved, which finally induced retinal detachment. To our best knowledge, this is the first case report of disseminated nocardiosis with ocular lesion in MG patients.
Ocular tissue is an unusual site for disseminated nocardiosis, and the ocular infection generally is diagnosed as local nocardiosis, presented with keratitis or endophthalmitis from ocular trauma or surgery [7]. Occasionally, the ocular infection might also be caused by hematogenous dissemination via the choroidal circulation [8]. The ocular nocardia infection in our patient may be caused by the hematogenous spread because the patient didn’t have eye trauma or surgery history, or had any abnormal signs on his eyeball. The prognosis of ocular nocardiosis is generally poor. Blindness was a common consequence, and ophthalmectomy was given in about 30% of patients. For these reasons, regular ophthalmologic screening should be performed in patients with suspected disseminated nocardiosis [8, 9]. In our patient, the ocular lesion located behind left eyeball which finally led to retinal detachment. After given suitable treatment, the ocular lesion completely vanished, but the vision was not restored.
Due to the paucity of trials, there are no formal guidelines to direct drug choice and treatment duration for nocardiosis. Most clinicians would agree that CNS nocardiosis warrants a long course of treatment, and 12 months is commonly recommended [10]. Empirical treatment of disseminated nocardiosis is usually with three antibiotics, including imipenem or ceftriaxone, TMP-SMX, and amikacin. TMP-SMX is thought as the cornerstone of treatment for nocardia infections, and it is also the drug of choice for cerebral nocardiosis due to its good penetration in the CNS. Other drugs, including meropenem, cefotaxime, minocycline, moxifloxacin, levofloxacin, linezolid, tigecycline, and amoxicillinclavulanicacid, are also used for the treatment [11]. Patients with nocardiosis often have underlying autoimmune disease or with immunosuppressive treatment. Therefore, the combination antibiotics is recommended in the beginning, and single drug can be maintained after the clinical symptoms are relieved [11]. Before the definitive diagnosis, our patient was treated empirically with moxifloxacin and imipenem, which were also suitable for treatment of nocardiosis. But the patient’s body temperature decreased temporarily, and exacerbated again some days later. It indicated that these drugs were not sufficient for the illness in our patient. After definitive diagnosis with nocardiosis, the patient received TMP-SMX in combination with ceftriaxone and etimicin therapy in short time, and then switched to TMP-SMX alone for one and half years.
Because of the nonspecific manifestations of nocardiosis, most patients with nocardia infection are not diagnosed in early stage of the disease, and it normally took from 42 days to 12 months for clear diagnosis after the appearance of symptoms [12, 13], which caused a lot of both physical and emotional burden to these patients. The prognosis of nocardiosis is depend on the location and severity of infection as well as the overall condition of the patients. The curable rate of pulmonary nocardiosis was about 90% with in time treatment, while the one-year mortality rate of patients with CNS involvement is high. The mortality in patients with solid organ transplantation from nocardiosis was 10-fold higher than those without [11, 14].
In general, Nocardia bacteria is opportunistic bacteria and mainly infects immunocompromised patients. Even though MG is an autoimmune disease with often immunosuppressive treatments, the nocardia infection was rarely observed in these patients. We then performed the literature review by searching the MEDLINE database using the key words “nocardia,” “nocardiosis, “and “myasthenia gravis.” To date, only 7 case reports of MG patients with nocardiosis from our literature study[15-20]. To further understand the disease process, we summarized the clinical characters of these patients which were listed in table 1. Interestingly, only one female was found, and the rest were male with median age at 59 years old. Among these MG patients, 3 patients also had thymoma, 1 patient had tuberculosis in the young period and 1 patient had Good’s syndrome. All the patients had been treated with glucocorticoids and other different immunosuppressant, such as tacrolimus and cyclosporine. 3 patients received thymectomy. Similar to these patients in the literatures, the patient in our report was a 66-years old man, and he was given glucocorticoid and azathioprine therapy for 8 months before he had nocardia infection. From the literatures and our case, the following factors maybe the preconditions for nocardia infections in MG patients. The primary factor was the usage of immunomodulator and/or immunosuppressive agents, which were consistent with the previous numerous literatures[11, 14]. The second factor was the age. These MG patients were all middle aged and even older people. According to the epidemiologic studies the peak age of MG patients was either 20-30 years or 50-60 years old. Given our finding that MG patients with nocardia infection was 49-79 years old, which was close to MG patients with age at 50-60 years old, and so the older patients with MG might be more susceptible to narcodosis. The last factor maybe the gender, which is based on that 6 out of 7 MG patients with nocardia infection was male. In sum, the old male MG patients with immunomodulator and/or immunosuppressive agents might be the susceptible population for nocardia infection.
Nocardiosis is a life-threatening infectious disease, diagnosis in early stage and appropriate antibiotic therapy is crucial for prognosis. Ocular involvement is rare in disseminated nocardiosis, patients who are suspected having disseminated nocardiosis should receive ophthalmologic screening. Neurological physicians should be aware of the nocardia infection in MG patients.