Intraoperative Diagnosis of a Rare Case of Arthropathy - A Case Report and Review of Literature.

INTRODUCTION: Alkaptonuria is a rare metabolic disorder of autosomal recessive pattern of inheritance caused due to homogentisic acid oxidase enzyme deficiency. As a result, polymers of homogentisic acid get deposited in excessive amounts in the connective tissues, leading to brownish-black pigmentation termed as ochronosis. As the disease progresses, chronic inflammation results in arthritis of large weight-bearing joints. CASE REPORT: A 70-year-old female patient presented with complaints of being non-ambulatory since the past 10 days. She gave a history of difficulty in walking for the past 10-15 years associated with pain in the right hip which did not respond to analgesics and physiotherapy. The radiological assessment revealed severe joint destruction of the right hip. The patient underwent a total hip arthroplasty. A provisional diagnosis of ochronosis was made intraoperatively which was later confirmed on histopathological examination of the tissue.
CONCLUSION: At present, there is still no known effective medical treatment to halt alkaptonuria entirely. Ochronotic arthropathy is usually managed conservatively. However, for severely involved hip joints, arthroplasty can provide extremely good results. Copyright: © Indian Orthopaedic Research Group.

It is important for an orthopaedic surgeon to have a high index of suspicion for other etiologies such as metabolic bone diseases in patients who do not fit into the characteristic clinical and radiological picture of common conditions causing hip arthritis.

Introduction

Alkaptonuria is a metabolic disorder of autosomal recessive pattern of inheritance. The pathogenesis of the disease revolves around the deficiency of homogentisic acid oxidase enzyme which is involved in the metabolism of tyrosine and phenylalanine. Due to this defect, homogentisic acid accumulates in enormous amounts in the connective tissue (especially cartilage) which leads to brownish-black pigmentation. These changes are called ochronosis. With the progression of the disease, the tissues get damaged due to chronic inflammation which further leads to degeneration and arthritis [1].

At present, there is no specific treatment for alkaptonuria and the accompanying ochronotic arthropathy due to the absence of large studies in the literature [2]. However, there are reports which suggest that the outcome of arthroplasty in ochronotic arthropathy is as satisfactory as in degenerative arthritis [3].

In this case report, we present a 70-year-old female patient with alkaptonuria, who underwent arthroplasty of the right hip due to ochronotic arthritis. The difficulties in clinching the diagnosis and during surgery are reported and discussed. The patient’s informed written consent was taken for print and electronic publication of this case report.

Case Report

A 70-year-old female patient presented to us with complaints of being non-ambulatory since the past 10 days. She gave a history of difficulty in walking for the past 10–15 years associated with pain in the right hip which did not respond to analgesics and physiotherapy. She also complained of mild pain in the left hip and both the knees. She did not have any history of trauma or fall. There was no other medical or surgical illness. Family history was insignificant. On examination, the right hip had a 2 cm shortening with the joint movements being painful and restricted. A flexion deformity of 10° was noted in the same hip. In addition, the right hip had a restricted abduction and adduction compared to the left hip. There was also a bilateral knee flexion and varus deformity of 10 degrees each. Clinically, we provisionally diagnosed the case as arthritis of the hip joint under evaluation.

The radiological assessment revealed severe joint destruction of the right hip with a fracture at the neck of femur. Femur head demonstrated irregularity and significantly narrowed hip joint space (Fig. 1).

Figure 1

Pelvis with both hips roentgenogram demonstrating bilateral hip arthritis with severe joint destruction of the right hip.

The left hip joint also showed narrowing of joint space. Both the knees revealed severe tricompartmental osteoarthritis (OA) (Fig. 2). The X-ray of the spine demonstrated fusion of vertebral bodies resembling a bamboo spine appearance (Fig. 3).

Figure 2

Bilateral knees with severe tricompartmental arthritis.

Figure 3

X-ray of the spine demonstrated fusion of vertebral bodies resembling a bamboo spine appearance.

On magnetic resonance imaging, significant bony destruction of the right femoral head-and-neck regions with superior subluxation of the right greater trochanter and femur was seen (Fig. 4). Inflammatory marrow changes in the residual upper femur raised the possibility of an associated osteomyelitis. Inflammatory or hemorrhagic fluid collections were seen in the acetabular fossa. The sacroiliac joint appeared normal.

Figure 4

MRI of the hip joint (coronal, axial, and sagittal sections).

The erythrocyte sedimentation rate (ESR) and C-reactive protein were within normal limits. Rheumatoid factor and HLA-B27 were negative as well.

Under local anesthesia and aseptic precautions, aspiration of the involved hip was done in the operating room and joint fluid sent for culture sensitivity and GeneXpert. The aspirate did not show any growth on culture. The results of the GeneXpert turned out to be negative as well.

A total hip arthroplasty was planned. Intraoperatively, on lifting the short external ro­tators, we found the joint capsule to be black. The capsule had lost its natural consistency and had turned hard and contracted. Moreover, the joint surfaces, ligaments, and tendons were blackish too with pieces of black cartilage. The capsule was excised posteriorly and the femur head was removed. Reaming of the acetabulum revealed poor bone quality. An uncemented acetabular cup was used (44 mm) with a ceramic liner (Fig. 5, 6).

Figure 5

Classic degenerative changes at hip joint.

Figure 6

Dark and thickened soft tissues.

After the reaming and broaching of the femoral canal, an uncemented femur stem (Smith and Nephew, cone 12/14, size 1) was inserted and the hip joint was reduced. There were no intraoperative or post-operative complications. The bone and soft-tissue specimens were sent for histopathological evaluation. The pa­tient was mobilized full weight-bearing on the 1st post-operative day and was discharged on the 3rd day.

Postoperatively, reexamination of the patient revealed brownish-black pigmentation of the ear pinna as well as the sclera (Fig. 7). The urine of the patient was also tested and it turned dark on standing for 24 h (Fig. 8).

Figure 7

Black pigmentation of the sclera ear pinna.

Figure 8

Urine turning dark on standing for 24 h.

On histopathological examination, the articular cartilage showed brownish-black pigmentation throughout, sparing only the part adjacent to the underlying bone. Soft-tissue demonstrated brownish-black fragments of pigmentation which were sharply defined and irregularly shaped. The surrounding tissue revealed fragments of non-viable bone, inflamed synovial tissue, foreign body type gi­ant cells, and fibroblastic proliferation with few hyalinized areas. The synovial lining was denuded. All of the features mentioned above are consistent with the diagnostic findings of ochronosis (Fig. 9).

Figure 9

HPE: Brownish-black pigmentation, foreign body type giant cells, and inflamed synovial tissue, all being typical findings of ochronosis.

The follow-up of the patient at 1 year revealed that her right hip pain had completely subsided along with a full range of motion. The Harris Hip Score of the patient had shown significant improvement from 32 preoperatively to 81 at 1 year follow-up. The patient was also counseled for a bilateral total knee replacement.

Discussion

Alkaptonuria is a rare disease which affects approximately 1 in 1 million people according to the statistics in the European countries [4]. However, there is no published literature on the incidence of the disease in India as very few of them have been reported. It is the first genetic disease described with autosomal recessive trait caused due to a mutation in the HGD gene on chromosome 3q which is responsible for the functioning of the enzyme homogentisate 1, 2-dioxygenase [1]. This enzyme breaks down homogentisic acid (HGA). The non-functioning defective enzyme causes accumulation of HGA in soft tissues over a period of time. The excess HGA is converted to benzoquinone acetic acid which, in turn, undergoes polymerization to form compounds which are similar to the pigment melanin. This leads to the dark pigmentation in these patients [5, 6, 7]. Ochronosis, being a musculoskeletal manifestation of alkaptonuria, affects the entire body causing brownish-black pigmentation of connective tissue, articular cartilage pathology, internal organ dysfunction, osteoporosis, and advanced arthropathy of the weight-bearing joints [6, 7].

The disorder is generally asymp­tomatic until the fourth decade when the joints start getting involved. The most common joint involved in ochronotic arthropathy is the knee. It is followed by hip, shoulder, lumbar intervertebral discs, and sacroiliac joints.

It is important to distinguish between ochronotic arthropathy, OA, and ankylosing spondylitis (AS) as they may resemble each other [8].

In ankylosing spondylitis, there is comparatively greater cervical rigidity with increased pain. Sacroiliac joint fusion, spinal ligaments and annular ossification, erosions and vertical, and thin syndesmophytes are characteristically seen in AS. ESR is also typically raised [9, 10].

Small joints of the hand are characteristically affected in OA. Progressive restriction of movement, stiffness, and syndesmophytes are not features of OA and help in differentiating it from ochronotic arthropathy and AS [8].

Table 1 differentiates between the characteristics of these disorders [11].

Table 1

Differentiating ochronotic arthropathy from ankylosing spondylitis and primary OA [11]

Another condition to be considered in the differential diagnosis is pigmented villous nodular synovitis of the hip. However, it most commonly occurs between the age of 20 and 40 years and is almost always monoarticular. Cystic bony erosions, hyperplastic synovium, and low signal intensity on both T1- and T2-weighted images are seen on magnetic resonance imaging. The tissues are pigmented brownish orange due to the deposition of hemosiderin. On histopathology, it shows fibrous stroma, hemosiderin deposition, giant cells, and histiocytic infiltration [12].

Thus, the diagnosis of ochronotic arthropathy is complex and may be made intraoperatively during the joint replacement surgery, as in our case.

This event also reestablishes the importance of a thorough general examination of all patients irrespective of the specific diagnosis and department. Unfortunately, this aspect of examination is neglected in many high turnover orthopedic departments. The peculiarity of our case was that the patient presented with a fracture of the femur neck in the absence of any trauma with a background of hip arthritis. To the best of our knowledge, such presentation has not been reported anywhere in the literature.

At present, there is still no known effec­tive medical treatment to halt the disease entirely [2]. Nitisinone is currently under evaluation for its use in alkaptonuria as it has demonstrated a decrease in the urinary excretion of HGA. It inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase which is responsible for the formation of HGA from 4-hydroxyphenylpyruvate.

In a recent study from the National Alkaptonuria Centre (United Kingdom), Ranganath et al. have demonstrated for the 1st time that nitisinone prevents the progression of alkaptonuria and arrested ochronosis in 39 patients over a 3-year period [13]. Vitamin C, Vitamin E, and N-acetyl cysteine are being assessed for their ability to prevent oxidation and polymerization of HGA and thus arresting the progression of the disease [14].

Ochronotic arthropathy is usually managed conservatively. However, for severely involved hip and knee joints, arthroplasty can provide extremely good results. There are no large published series regarding the results of arthroplasty in alkaptonuria, the reason for this being the very rare occurrence of this disease. However, the limited number of case reports in literature demonstrates promising results with respect to pain management and preservation of joint mobility (Fig. 10).

Figure 10

Post-operative X-ray of the patient – uncemented total hip arthroplasty.

Conclusion

With the lack of medical management preventing the progression of joint destruction, arthroplasty proves to be a highly effective management surgery for ochronotic arthropathy in alkaptonuria pa­tients.

Ochronotic arthropathy is a manifestation of a rare disease and therefore likely to be missed in an orthopedic clinic during the initial diagnosis. High index of suspicion is required for clinching the diagnosis and thus initiating early medical and necessary surgical management.