Background

The clinical and epidemiological characteristics of Vibrio vulnificus infection were first reported in 1979 by Blake et al. V. vulnificus is a slightly halophilic Gram-negative bacillus with an optimal salt concentration of 2–3% that lives in seawater and brackish water [1]. V. vulnificus infections mainly occur in western Japan during the summer, and it is considered one of the most dangerous waterborne pathogens, with a reported fatality rate of 50% [2]. Human infection occurs by eating raw or insufficiently heated food contaminated with V. vulnificus, exposure to seawater, or wounds inflicted by marine animals. V. vulnificus infection can result in fatal sepsis in patients with underlying diseases, such as preexisting liver disease, hemochromatosis, or immunodeficiency. To the best of our knowledge, there are no case reports of primary biliary cholangitis (PBC) associated with V. vulnificus infection. Herein, we report the case of a patient with PBC and sepsis caused by V. vulnificus infection sustained through shrimp shelling.

Case presentation

The patient was an 82-year-old Japanese Asian woman with no comorbidities, relevant family medical history, alcohol consumption, or known allergies. No previous liver disease or abnormal liver function tests were noted. However, she had been a smoker of 20 cigarettes per day until 3 years prior. After mountain climbing on 23 and 24 July 2012, she experienced numbness and pain in the right arm. On 25 July, she developed general malaise. Since her symptoms did not improve by the morning of 26 July, she visited a private hospital with facial pallor, poor dietary intake, redness, mild swelling, and pain in the right arm. She was in circulatory shock with a blood pressure of 60/48 mmHg, and was later transported by an ambulance to Fukuoka University Hospital.

Her physical findings on admission were as follows: body height, 158 cm; body weight, 51.0 kg; body mass index, 20.43 kg/m2; conscious and coherent; blood pressure, 66/33 mmHg; pulse rate, 91 beats per minute (bpm; regular); respiratory rate, 22 breaths/minute; SpO2, 97% (room air); body temperature, 37.7 °C; and redness and swelling extending from the medial part of the right upper arm to the right elbow and forearm (Fig. 1). Blood tests showed high levels of inflammation (Table 1), and computed tomography of the upper arm revealed adipose tissue turbidity (Fig. 2). We suspected septic shock, with the infection originating in the upper arm.

Fig. 1
figure 1

Skin rash in the right upper arm. Redness and swelling are observed above the right elbow on day 1. The area is warm to touch

Full size image
Table 1 Blood examination results on day 1
Full size table
Fig. 2
figure 2

Computed tomographic examination of the right upper arm. A soft tissue opacity is seen in the right arm

Full size image

First, to stabilize blood pressure, we rapidly administered 1000 mL of lactated Ringer’s solution, an initial dose of meropenem 1.0 g after blood culture specimens were collected, and noradrenaline at 0.2 µg/kg/minute. Then, under local anesthesia, a 5-cm incision was made distally from the medial right upper arm and proximally from the medial right cubital fossa. The color tones of the subcutaneous fat and fascia were normal, and we suspected cellulitis rather than necrotizing fasciitis. For the septic shock, we continued to administer meropenem (3.0 g/day) for 12 days, with linezolid (1.2 g/day) for 5 days and immunoglobulin (5 g/day) for 3 days via intravenous injection. On day 2 of hospitalization, a blood culture detected Gram-negative bacilli (Fig. 3a), and linezolid was discontinued. On day 5 of hospitalization, V. vulnificus was identified by blood culture, and we added minocycline (100 mg) twice daily for 8 days, to which V. vulnificus was susceptible (Fig. 3b). Subsequently, the inflammatory findings rapidly improved; the patient’s C-reactive protein levels dropped from 9.3 to 1.1 mg/dL in 9 days. Although there was no history of seafood intake or contact with seawater, we learned that the swelling developed in the right hand 1 day after she had shelled a large number of raw shrimp for cooking, and the swelling spread to the trunk. Therefore, we believed that the route of V. vulnificus infection was through minor skin wounds inflicted by shrimp shells.

Fig. 3
figure 3

Bacteriological findings. a Blood culture Gram stain; b antibiogram of V. vulnificus. ABPC ampicillin, CEZ cefazolin, CMZ cefmetazole, CTX cefotaxime, MEPM meropenem, MINO minocycline, LVFX levofloxacin

Full size image

On day 11 of hospitalization, the treatment was switched to oral levofloxacin (500 mg daily), as the redness and swelling in the upper arm had improved. After 7 days, drug-induced thrombocytopenia was observed, and levofloxacin was discontinued. No recurrence was observed, and the patient was discharged on day 28 of hospitalization (Fig. 4).

Fig. 4
figure 4

Disease course after admission. Nad noradrenaline, IVIG intravenous immunoglobulin, LZD linezolid

Full size image

During the course of hospitalization, persistent elevation of serum γ-glutamyl transpeptidase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels suggested liver disease. Blood tests performed on day 5 of hospitalization showed positivity for anti-mitochondrial M2 antibodies (Table 2), and abdominal echography showed a pattern of chronic liver disease, leading to the diagnosis of PBC. Since the liver damage was mild, we started to administer ursodeoxycholic acid (600 mg/day). On follow-up with the practitioner, we received no reports of exacerbations.

Table 2 Blood examination results on day 5
Full size table

Discussion and conclusions

In the present case, the cause of sepsis was initially unclear because the patient had no relevant medical history or underlying disease. However, blood culture revealed a causative organism, V. vulnificus, and the history of shrimp shelling was identified. We thought the fungus entered through a small wound and became the source of infection. Moreover, V. vulnificus infection tends to accompany liver disease, and persistent elevation of serum γ-glutamyl transpeptidase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels suggested liver disease, diagnosed as PBC in our patient. This is an interesting case study because we could not find any similar case reports.

V. vulnificus is a Gram-negative bacillus that causes wound infections and sepsis in some patients. The outcomes of V. vulnificus infection tend to be serious in men, and in middle-aged and older patients (> 40 years of age), particularly those with underlying diseases, such as liver disease, diabetes, immune disorders, elevated serum iron concentration, and cirrhosis (mainly alcohol induced) [2]. V. vulnificus infection is characterized by a short incubation period, typically within 24 hours of exposure. Moreover, since this bacterium can cause severe infections, such as bacteremia and wound infections, prompt initiation of antibacterial therapy is essential. Therefore, if an infection is suspected, particularly in high-risk patients, it is crucial to identify this bacterium accurately and rapidly in clinical practice [2]. In one report, regarding the rates of sepsis and wound infection, V. vulnificus caused wound infections and bacteremia in 62 patients over the course of 1 year in Israel. Among them, 57 patients developed cellulitis, four developed necrotizing fasciitis, and one developed osteomyelitis. The fatality rate of V. vulnificus infection has been reported to be 20–50%, and no deaths were observed in this particular report [1].

The proliferation of V. vulnificus is influenced by water temperature. V. vulnificus accounted for approximately 8% of the aerobic bacteria in samples collected from the Chesapeake Bay between April 1991 and December 1992. It was not detected in February or March (water temperature < 8 °C) but was detected in 80% of the samples in May, July, September, and December (water temperature > 8 °C) [3]. Regarding the salt concentration of the water, when the influx of freshwater from the Mississippi River reduced the salt concentration at the Mississippi shoreline, V. vulnificus became temporarily undetectable in this area. Therefore, salt concentration greatly influences the growth of V. vulnificus [4]. In the present case, although the location at which the shrimp were caught was unknown, the disease onset in July did not contradict the biology of V. vulnificus.

PBC, which is an autoimmune disease associated with environmental and genetic factors, was first reported by Addison et al. in 1857; however, its exact cause remains unknown [5]. A study of 1032 patients with PBC revealed that it is more common in women and is sometimes accompanied by other autoimmune diseases such as Sjögren’s syndrome and Raynaud syndrome [6]. A family history of PBC, smoking, and history of urinary tract infections are also commonly reported. Furthermore, it has been suggested that in urinary tract infections, Escherichia coli can disrupt immune tolerance, leading to the development of PBC [6, 7]. In the present case, PBC was revealed by blood test on the fifth day of onset. It is possible that V. vulnificus infection occurred after the patient originally had PBC, or that PBC developed after V. vulnificus infection. It is also possible that the two diseases coincidentally overlap. However, there are no precedents for either of these possibilities, and we cannot discuss these possibilities at this time.

In conclusion, the lessons learned from this case suggest that it is useful to evaluate patients with V. vulnificus infection for the presence of undiagnosed liver disease, such as asymptomatic PBC. In addition, a detailed history regarding V. vulnificus infection should be obtained because shelling of crustaceans is a potential source of infection.