The not so familiar silent joint killer: Ochronosis – A case report with review of literature

Gowtham Bandi; Ram Kartheek Randhi; Jameer Shaik; Varun Kumar Paka; Raviteja V S. Seerapu

doi:10.4103/jodp.jodp_32_22

CASE REPORT

Year : 2022 | Volume : 5 | Issue : 3 | Page : 185-189

The not so familiar silent joint killer: Ochronosis – A case report with review of literature

Gowtham Bandi¹, Ram Kartheek Randhi¹, Jameer Shaik², Varun Kumar Paka³, Raviteja V S. Seerapu¹
¹ Department of Orthopaedics, GEMS, Srikakulam, India
² Consultant Orthoapedic Surgeon, Department of orthopaedics, Chaitra Hospital, Eluru, India
³ Department of Orthopaedics, NIMRA Institute of Medical Sciences, Vijayawada, Andhra Pradesh, India

Date of Submission	24-Mar-2022
Date of Decision	05-Jun-2022
Date of Acceptance	07-Jun-2022
Date of Web Publication	1-Sep-2022

Correspondence Address:
Ram Kartheek Randhi
Department of Orthopaedics, GEMS, Srikakulam, Andhra Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jodp.jodp_32_22

Abstract

Ochronosis is rarely considered a cause for knee synovitis due to its rare occurrence. It starts affecting the joint from the third decade onward causing premature joint damage. The damaged joint and surrounding tissue present as blackish decolorated mass and can surprise the operating surgeon, unless diagnosed beforehand. Prior diagnosis helps both the anesthetist and operating surgeon to better handle the associated complications of ochronosis during surgery. Diagnosis is essentially based on prior knowledge of the disease and its markers. Here, we report a rare case of ochronosis of the knee that was treated elsewhere previously as tuberculosis of the knee. A history evaluation along with intraoperative findings helped arrive at the possible diagnosis of ochronosis. Total synovectomy was done. Postoperative improvement of visual analog scale score was significant and the patient was satisfied with the pain relief attained through treatment. Early diagnosis and timely management is critical to avoid unwanted complication related to both anesthesia and surgery pertaining to the disease. Knowledge of skin markers and urine darkening helps in identifying the disease early.

Keywords: Alkaptonuria, benzoquinone acetate, ground pepper sign, homogentisate 1,2-dioxygenase, Osler's sign

How to cite this article:
Bandi G, Randhi RK, Shaik J, Paka VK, S. Seerapu RV. The not so familiar silent joint killer: Ochronosis – A case report with review of literature. J Orthop Dis Traumatol 2022;5:185-9

How to cite this URL:
Bandi G, Randhi RK, Shaik J, Paka VK, S. Seerapu RV. The not so familiar silent joint killer: Ochronosis – A case report with review of literature. J Orthop Dis Traumatol [serial online] 2022 [cited 2023 Jun 6];5:185-9. Available from: https://jodt.org/text.asp?2022/5/3/185/355245

Introduction

Alkaptonuria popularly referred to as the black bone disease^[1] is a rare inborn error of metabolism. It is characterized by the deficiency of homogentisate 1,2-dioxygenase enzyme necessary for breakdown of homogentisic acid (HGA) in the tyrosine breakdown pathway.^[2] HGA excreted in urine stains nappies dark in new born. Tissue deposition of HGA occurs during later part of life. It may manifest as aciduria, ochronosis, or osteoarthropathy depending on the age of presentation.^[3] Deposition of HGA until the third decade is relatively low due to efficient clearance by renal system. From third to fifth decades, deposits (ochronosis) in eye, ear, and nose are common. It affects organs such as the skin, heart, kidney, large joints, and glands.^[4] It is associated with deposition of stones in the kidney, gallbladder, salivary glands, and prostate. Osteopenia and bone fractures and rupture of tendons and ligaments are the other possible features related to alkaptonuria. Osteoarthropathy secondary to alkaptonuria is rarely diagnosed. It is most of the times misdiagnosed and treated as rheumatoid or osteoarthritic disease. Intraoperative presentation of blackening of the joint surface is what that draws the attention of the surgeon to establish the disease. Here, we present a case report of the knee arthritis secondary to alkaptonuria.

Case Report

A 51-year-old male agricultural laborer attended our clinic 1 year back with a 4-year complaint of right knee pain, swelling, and stiffness, which were treated elsewhere with antituberculous treatment (ATT) for 1 year. Persistence of pain and swelling even at the end of ATT treatment compelled the patient to seek second opinion at our institute 1 year after his ATT regimen.

According to his history, right knee pain started insidiously 4 years back with intermittent swelling of the joint that hampered his daily activity. Courses of analgesics and physiotherapy did not offer him any comfort. The patient also had a history of chronic low back ache of 10-year duration associated with morning stiffness with worsening throughout the day during activity. No constitutional symptoms were reported. There was no history suggestive of any contact tuberculosis. On physical examination of the right knee, it was found to be swollen, tender with a fixed flexion deformity of 10°, and further active flexion possible up to 120°. Joint line tenderness with painful terminal range of active movements was present with no signs suggestive of ligamentous laxity.

X-ray of the knee showed mild arthritic changes [Figure 1]a. Diffuse severe osteopenia with mild lumber scoliosis and loss of lordosis in lumbar spine along with narrowing of calcific disk spaces in the dorsal and lumbar spine were noticed in spine X-rays [Figure 1]b. Chest X-ray was interpreted as normal. Laboratory investigations such as C-reactive protein, erythrocyte sedimentation rate, and complete blood profile were all within normal range. Magnetic resonance imaging of the right knee showed mild joint effusion and synovial thickening, Grade II articular changes, mucoid degeneration of anterior cruciate ligament, and lateral meniscus degeneration with complete tear and intra-articular loose bodies [Figure 2]. Results of the knee arthrocentesis were nonspecific and inconclusive.

Figure 1: Preoperative radiological images: (a) X-ray of the knee suggestive mild degenerative changes with narrowing of the joint space; (b) X-ray of the spine showing diffuse severe osteopenia with mild lumber scoliosis and loss of lumbar lordosis and narrowing calcific disk spaces in the dorsal and lumbar spine

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Figure 2: Preoperative magnetic resonance images of the knee: (a) sagittal and (b) axial cuts showing synovial thickening with mild degenerative changes

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The patient had a history of spontaneous rupture of the right and left Achilles tendon, which occurred 8 and 7 years back, respectively. On both occasions, repair of the tendons was achieved with subsequent uneventful healing. The patient had an episode of renal colic (renal stones) 5 years after onset of low back ache. He also had a complaint of bilateral hip pain, intermittent in nature of 2 years' duration. The patient had been on antihypertensive medication for the past 10 years.

Involvement of the spine and knee at this young age along with spontaneous tendon ruptures and renal colic pointed toward a pattern favorable for systemic disease. Characteristic patterns in the spine led to the suspicion of ochronosis. A detailed head-to-toe examination of the patient for markers of underlying disease revealed dark pigmented patches in the sclera (Osler's sign) of both the eyes [Figure 3]a. Ear conche was unusually hard and so was the tip of the nose [Figure 3]b and [Figure 3]c. The patient's urine turned dark on long standing and on addition of alkali substance, which confirmed the diagnosis of alkaptonuria [Figure 4]. Qualitative ferric chloride test was positive with high HGA levels of 0.84 in 24 h. [Table 1] shows results/findings of some of the relevant investigations performed on the patient before surgery.

Figure 3: Important markers of ochronosis: (a) Osler's sign - dark pigmented patches in the sclera of both the eyes (b and c) – characteristic hardening of the ear conchae

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Figure 4: Patient's urine sample (a) that turned dark (b) on long standing which is commonly referred to as Cola-colored urine – characteristic of ochronosis

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Table 1: List of some important investigation with their result/findings

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The patient was advised total synovectomy as the cartilage damage was minimal and did not necessitate the need for total joint replacement at this stage. Thorough preoperative evaluation was done to assess the rigidity of the cervical and lumbar spine. Preoperative chest physiotherapy was advised to maintain the chest compliance. Arrangements were made for flexible guided intubation and awake fiberoptic intubation was kept as stand by option. The anesthetist faced marked difficulty in administering spinal anesthesia. Repeated attempts were futile and compelled them to resort to paraspinous or paramedian approach to spinal anesthesia. Tranexamic acid was administered prior to incision in anticipation of increased blood loss associated with synovial hypertrophy. An anterior midline knee incision longer than usual was made. Through a medial parapatellar approach, the joint was reached. Care was taken to carefully retract the patellar tendon without everting it to avoid rupture. Inflamed synovial tissue was excised. Intraoperatively, brownish black discoloration of bone and soft tissue in and around the knee was evident [Figure 5]. There was visible eburnation of cartilage with black pigmentation of tissue.

Figure 5: Intraoperative images: (a-e) Classical brownish black discoloration of bone and soft tissue in and around the knee suggestive of ochronosis. (f) Tissue specimen obtained through synovial biopsy shows alternating black, dark brown and grayish brown areas consistent with features of ochronosis (g and h) intraoperative positioning of limb for incision

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Gross appearance of the tissue sent following synovial biopsy was consistent with alternating black, dark brown, and grayish brown areas [Figure 5]f. Microscopic examination of this tissue showed a polypoid synovial mass with focal areas of hyperplasia of the lining epithelium [Figure 6]. Subepithelial fibrocartilaginous tissue showed multiple brown shards (brown brittle pigmented cartilage) embedded in the stroma. Lymphoid aggregates and foreign body giant cell findings were consistent with the diagnosis of ochronosis. Synovial tissue sent for culture was negative for mycobacterial growth. Postoperative period was uneventful. There was reasonable improvement in the postoperative visual analog scale scores of the patient. The patient was followed up for a period of more than 1 year. There was a significant improvement in the patient's pain relief attained at the end of follow-up. The range of movements in the knee was near normal compared to the opposite unaffected side. The patient was able to carry out his activities of daily living. No recurrence was noticed during the entire period of follow-up.

Figure 6: Microscopic examination photographs of the tissue (a and b) showing a polypoid synovial mass with focal areas of hyperplasia of the lining epithelium. Subepithelial fibrocartilaginous tissue showed multiple brown shards (brown brittle pigmented cartilage) embedded in the stroma. Lymphoid aggregates, foreign body giant cell reactions, and proliferating capillaries

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Discussion

Alkaptonuria is one of the first diseases in humans to be identified as having Mendelian recessive inheritance.^[5] Worldwide, the prevalence of the disease is one in 2.5–10 lac cases. Most of the reported cases are from Slovakia, the Dominican Republic, India, and Jordan.^[6] Low levels or absence of homogentisic dioxygenase enzyme lead to accumulation of HGA in the body.

Three distinct evolutionary stages of the disease are aciduria, ochronosis, and ochronotic osteoarthropathy.^[7] Aciduria is the result of oxidization of HGA pigment to benzoquinone acetate (BQA), which forms a melanin-like polymer that slowly turns urine black/dark or stains the nappies.^[8] By the age of 20–30 years (ochronosis), BQA accumulates in the connective tissue (intra- and extracellularly) of the ears, eyes nose, body fluids, large gut, cyclic vomiting syndrome, and kidneys.^[9],[10] Tendon ruptures, fractures, and osteopenia of the bone are the other associated features.

Arthropathy, tendinopathy, and osteopenia/osteoporosis are the musculoskeletal manifestations related to the disease. In 40 to 60 years age group, early joint degeneration sets in due to deposition of BQA in hyaline articular cartilage of most of the joints.^[3] Low back ache (dorsolumbar with disk calcification and vertebral porosis) is an initial manifestation of the disease, followed by involvement of the large weight-bearing joints. It commonly affects hip followed by knee and shoulder. Most of the patients will end up needing a joint replacement surgery at an early age. Multiple arthroplasties are usually needed in these patients. Aspiration of joints with effusion usually reveals black floating particles referred to as “ground pepper sign.”

Complete capsule excision during surgery is necessary to prevent local recurrence. Total synovectomy in these patients is usually associated with high blood loss during and after surgery. This may be attributed to the hypertrophied synovium and can be managed by administration of tranexamic acid during surgery and through adequate blood reserve for surgery. Deposition of BQA leads to blackening of the cartilage and softening of the bone, but none of this seems to affect the bone healing or union.^[11],[12] Internal fixation can be opted for fracture management in these patients without the fear of delayed union. Uncemented prosthesis is not a contraindication as bone in-growth is unaffected by this disease process.^[13]

Synovectomy may suffice in the initial stages with synovial thickening and minimal cartilage involvement. Severely damaged joints in end-stage disease of alkaptonuria are better managed by total joint replacement.^[14] It is always better to plan for a relatively longer incision for these patients than what is usually preferred by the surgeon for routine replacement surgeries. Cemented total knee arthroplasty is preferred as it has a better survival rate than the cementless option.^[15] Posterior cruciate ligament substituting total knee arthroplasty is preferred.^[16] There have been reports of rupture of quadriceps tendon during patellar retraction. Patellar resurfacing is preferred, but alternatively careful patellar retraction alone or else eversion with precaution may suffice.^[17]

In the spine due to reduction of the effective spaces, drug doses should be judiciously calculated to avoid higher levels of spinal anesthesia. As the chances of failure of spinal anesthesia are high, arrangements should be made for flexible guided intubation or for awake fiberoptic intubation.^[18] Kozanhan reported in his case report that spinal anesthesia could not be given because of difficulty in positioning due to deformities and widespread calcifications. Ultrasound-guided spinal anesthesia may be opted in such situations with superior success rates.^[19] Jain et al. reported a case of cardiac stroke that developed on the third postoperative day after total knee arthroplasty with the patient being revived successfully. As chest compliance is reduced in these patients, chest physiotherapy and intense respirometry are better advised for about 2 weeks preoperatively.^[20]

Low-protein diet with restriction of tyrosine intake and addition of ascorbic acid to diet may be beneficial in the patients. HGA deposits render the bone matrix unresponsive to bisphosphonate therapy.^[21] Tranexamic acid aids in reducing the intra- and postoperative blood loss associated with alkaptonuria. Do not hesitate to use bone cement and one should be careful when making the bone cuts as the bone is soft in these patients. Preoperative cardiac clearance is essential to rule out calcified cardiac valve disease. Arthroscopy can delay the need for arthroplasty by bringing an improvement in range of motion in the joints and relieving the symptoms.^[22]

Conclusion

Alkaptonuria is a rare disease with multisystemic involvement. Debilitating physical deformities in these patients almost always necessitate joint replacement surgeries at a very younger age. These surgeries always pose significant problems to both the surgeon as well the anesthetist. This warrants the need for high degree of suspicion to ensure early diagnosis, prevent unwanted therapies/procedures, and avoid delay in management. Proper knowledge about the cutaneous markers and darkening of urine are minimal requirement to arrive at a possible diagnosis. X-ray of the involved joint and spine further strengthen the diagnosis through relevant characteristic findings. Diagnosis will help us in planning proper anesthetic and surgical techniques. It allows us to tackle anticipated complications during intra- and postoperative periods. There is a need to set up multicentric studies on the subject and perform more studies on this topic.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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