Rare Pseudotumor in Ceramic-On-Ceramic Total Hip Replacement with Concomitant Fungal Periprosthetic Joint Infection: A Case Report

Background

Total hip replacement (THR) is a commonly performed treatment for severe osteoarthritis, but it is not free of complications, which can lead to early failure of the components [1,2]. In this report we present the case of a woman who unfortunately suffered 2 severe but rare complications of THRs: a periprosthetic fungal infection, which may have promoted the development of an extremely rare pseudotumor on a ceramic-on-ceramic (CoC) THR. Fungal periprosthetic joint infections (PJI) are rare and devastating infections, which have been growing in numbers and are usually related to chronic comorbidities like diabetes or immunosuppression. They also have higher incidence in patients who receive long-term antibiotics in the 3 months before surgery, usually given as an attempt to treat a previous bacterial PJI [1,3]. In the literature, pseudotumors are defined as non-neoplastic and non-infectious masses resulting from a circumscribed fibrous exudate of inflammatory origin, fluid accumulation, or other causes [4]. These are rare complications with a high probability of inducing early failure of the prosthesis. These have been associated in many cases with metal-on-metal (MOM) and sometimes with metal-onpolyethylene total hip replacements (MOP), with only 1 other published case of a pseudotumor in a ceramic-on-ceramic THR [5–7]. The aim of this case report is to raise awareness of pseudotumor and its possible association with fungal PJI. We describe the second ever reported pseudotumor in a CoC THR and propose a hypothesis for further research into whether a fungal infection could react with the CoC bearing surfaces of the THR, increasing the chances of pseudotumor formation.

Case Report

In early 2016, a 63-year-old woman presented to our orthopedic clinic with severe left hip pain and reduced range of motion, which was interfering with her daily activities. On plain pelvis X-ray, signs of osteoarthritis were clearly shown. At that time, the patient was actively working, fully independent, and non-diabetic, with a past medical history of hypertension, hypercholesterolaemia, Duputryen’s contracture, appendectomy, oophorectomy, haemorrhoidectomy, and right THR. She was a non-smoker and an occasional drinker. Therefore, she underwent an elective left total hip replacement, for which we implanted a Trilock femoral component size 6, a Biolox Delta ceramic head size 36+8.5 mm, a Pinnacle acetabular component size 52 mm inner diameter, and a Biolox Delta ceramic liner size 52 mm outer diameter and 36 mm inner diameter. All the components were manufactured by DePuy Synthes, Raynham, MA, USA (Figure 1). The procedure was performed without any acute complications, and her postoperative rehabilitation was uneventful.

In May 2018, she presented to her general practitioner (GP) with a suspicious widespread, foul-smelling, white lesion on her tongue, which did not bleed when scratched. Her GP diagnosed her with a fungal infection and started oral antifungal therapy and referred her to the Ear, Nose, and Throat) (ENT) Department. On attendance, the lesion did not resolve after 1 course of fluconazole and a second course of Mycostatin. Therefore, the ENT surgeon, who believed it was a deep-site infection on the floor of the mouth, arranged a biopsy. The biopsy, taken from the anterior and middle part of the tongue, showed squamous cell epithelium with hyperkeratosis, acanthosis, and subepithelial mild chronic inflammation, without signs of fungal infection on periodic acid Schiff (PAS) stain. These results were as expected since she had already received 2 cycles of antifungal medication, and we wonder if this event could be the related to the later PJI.

During 2019, our patient was admitted due to thigh-to-calf leg swelling, with severe tenderness on the deep calf area and cramping sensation. Deep vein thrombosis was suspected; therefore, an US Doppler scan of the deep venous system was performed, which showed a 12.7×5-cm mass in the iliac region lateral to the left hip, which was thought to be a hematoma (Figure 2). She also had non-patent, non-compressible superficial and common femoral veins, suggesting deep vein thrombosis (DVT). The popliteal vein was patent and compressible, but the external iliac vein was not visualized. Following this finding, a CT scan of the thorax, abdomen, and pelvis (CT-TAP) with contrast was performed due to concerns of malignancy since the patient had an unprovoked DVT and a mass in the hip area. The CT-TAP showed no signs of malignancy and confirmed that the DVT had its origin in the external iliac vein. She was treated only with oral anticoagulant medication, since no hematological pathology was detected. Few months later, the patient was still suffering from left thigh-to-calf swelling, regardless of the ongoing anticoagulation and compression stockings. Following this, a CT venogram of the leg was performed (Figure 3), which showed another collection, this time 10×6×7cm, and no signs of DVT. For further screening, an ultrasound and magnetic resonance venogram was performed, to further evaluate the mass next to the THR. At the same time, to treat the long standing DVT, an external iliac vein stent was inserted (Figure 4, arrow 1).

Soon thereafter, an ultrasound was performed due to suspicion of a pseudotumor. A second MRI with MARS views was performed by request of the orthopedic consultant, confirming a pseudotumor in November 2020.

With this information, our orthopedic consultant performed a revision surgery of her left THR on 24 February 2022, which revealed a large pseudotumor. The bearing was exchanged for a ceramic-on-polyethylene bearing because the small ceramic debris that this prothesis created could have created the inflammation necessary to form a pseudotumor. While the friction of 2 hard surfaces like ceramic-on-ceramic can cause debris, a hard surface like ceramic will not crumble against a soft surface like polyethylene [8]. The pseudotumor was debulked but not completely excised due to the risk of iatrogenic injury to adjacent neurovascular structures (Figure 4, arrow 2). Specimens were sent for microbiology culture, which was positive for Candida parapsilosis. Therefore, she was kept for observation for 3 weeks due to suspicion of contamination of the specimen, but since she showed no signs of infection nor raised inflammatory markers, she was discharged without antibiotics, with close follow-up. The pathology report confirmed an aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL), typical for pseudotumors [4]. The sample was sent to a specialist musculoskeletal pathology laboratory, which confirmed the diagnosis (Figures 5–7). Several weeks after the revision surgery, she had an episode of left-hip dislocation, which was reduced. She also developed a rash with severe left-leg swelling, believed to be an adverse reaction to her direct oral anticoagulants (DOAC) for DVT prophylaxis. Almost 2 months after surgery, the wound created a sinus, which was continuously oozing. After discussion with the patient, 2 different DAIR procedures were performed. Because the infection was initially suspected in the acute postoperative period due to positive intraoperative cultures and was also an early-presentation PJI, since it was within 3 months after the surgery. It is also important to mention that the presence of sinuses is considered a contraindication by some authors, but there is no consensus on this topic. The sinus was excised as part of the procedure [9]. Multiple samples were taken for microbiology culture, which confirmed the Candida parapsilosis infection and detected a new superinfection with Staphylococcus aureus. She was treated with 6 weeks of IV antibiotics and IV antifungal therapy and offered a 2-stage revision, as it has been proven to be the definitive treatment for fungal PJI [10]. However, due to the patient’s personal circumstances, she declined further surgery. She is currently on long-term oral anti-fungal medication, the wound has a long-term draining sinus, from which multiple cultures have been extracted and after 12 weeks of IV and oral antibiotics, only Candida parapsilosis can be isolated. The option of 2-stage revision is still a possibility in the future.

Discussion

Fungal PJI are rare and can be difficult to diagnose. They account for approximately 1% of the total number of PJIs [1]. In addition to this, they are usually slow-developing infections, taking on average 86 months to present symptoms according to some minor studies and systematic reviews, and blood inflammatory markers are rarely elevated [11]. In our case, the fungal PJI did not show any symptoms before the joint was revised, with the pseudotumor, leg swelling, and pain being the main indications for the revision 6 years after the primary procedure. Moreover, even after obtaining a revision sample with a growth of Candida parapsilosis, the final diagnosis was challenging, since the patient had no symptoms and had normal blood markers. It is difficult to determine exactly when the infection of the prosthesis occurred, including if the infection occurred intraoperatively. Our patient had a strange suspected deep fungal infection in her oral cavity 2 years after the primary procedure, for which the ENT consultant never found a cause, since the teeth seemed unharmed and she had undergone antifungal therapy before the biopsy. We speculate that the oral fungal infection was due to an asymptomatic candidemia, creating hematological spread of the disease, or perhaps the buccal deep-seated infection infected the prosthesis through a similar pathway. Other cases of asymptomatic candidemia and cases of candidemia related to prostheses have been described before. How an otherwise healthy woman suffered such a severe infection usually related to polymorbid or immunosuppressed people remains a mystery [12,13].

Looking at the main premise of our case report, we have would like to introduce the hypothesis that our novel, second case ever described, finding of a pseudotumor in a CoC THR, was promoted by an interaction of the fungal species with the ceramic components of the liner. The exact pathophysiology of pseudotumor formation in this case is still uncertain. Pseudotumors have a histopathological presentation similar to that of an aseptic lymphocytic vasculitisassociated lesion, which can be related to metal hypersensitivity, unlike in our case, or a reaction to excess wear debris, which we can presume is our case, since there is no metal present in the contact surfaces of the CoC THR [7]. According to the FDA, free-metal ions might play an important role in this [5]. Pseudotumors are common in metal-on-metal (MOM) hip replacements, having an incidence rate of around 32%, depending on the study. There is also a wide array of reported pseudotumors in metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP), but there is only 1 other case of pseudotumor in a ceramic-on-ceramic (CoC) THR [7]. The main question regarding CoCs is how a pseudotumor could be created in a prosthesis with low capacity to shed metal. We believe that ceramic could also create this local reaction, as reported previously [7].

Although the statistical likelihood of having 1 rare complication and 1 extremely rare complication of total hip replacements in the same patient suggests an association between them, we have not found any research supporting this. Candida parapsilosis tends to create simple low-volumes biofilms, but there is no research on how these biofilms interact with the erosion of ceramic surfaces, or any surfaces at all [13].

Finally, this case report also describes an interesting symptom of pseudotumor formation, which is related to the mass effect, compressing other tissues. In this case, compressing the femoral vein produced a large unprovoked DVT in an otherwise healthy patient, which occurs by interfering with the principles of the Virchow triad, as reported previously [14].

Conclusions

This case report documents for first time the presence of a pseudotumor with a concomitant fungal PJI on CoC THR. Although it is unlikely for a person to develop 2 rare complications together without them being connected, we were unable to draw any definitive association due to the uniqueness of the case. Therefore, we would like to encourage more research on how Candida species react with ceramic surfaces or wait for more case like this to be reported. In this case report we also tried to raise awareness about the etiology, pathophysiology and symptoms of pseudotumors, as well as the behavior of fungal infections in prostheses, which although rare, are growing in numbers.