Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online:210
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 31  |  Issue : 2  |  Page : 138-140

Gout as a consequence of bone healing: A diagnostic dilemma


Department of Anaesthesiology, Division of Pain, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Web Publication6-Sep-2017

Correspondence Address:
Rajeev Kumar Dubey
Department of Anaesthesiology, Division of Pain, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpn.ijpn_42_17

Rights and Permissions
  Abstract 

Diagnosis of acute gout remains a diagnostic challenge if associated with trauma, and may easily be mistaken as cellulitis or septic arthritis. Gout is an inflammatory arthritis that is triggered by the deposition of sodium urate crystals within the joints and soft tissues, and is frequently associated with hyperuricemia. Hyperuricemia may arise in a wide range of clinical situations that cause overproduction or under-excretion of uric acid, or a combination of both. As uric acid is the ultimate breakdown product of purine nucleotide degradation in humans, any increase in purine production due to accelerated cell turnover may precipitate an acute attack of gout. Gout may be precipitated by conditions such a trauma, surgery, diuretic therapy, or ethanol intake. All predisposed individuals such as those with hypreuricemia, hypothyroid etc. with trauma and bone fractures should be observed for precipitation of acute gouty arthritis. Bone healing after a fracture may also lead to acute gout. Healing of a fractured bone, through multiple mechanisms, can precipitate acute gout, particularly in the presence of certain predisposing factors such as hypothyroidism, pre-existing hyperuricemia or tissue hypoxia. Acute inflammation and pain, if resistant to non-steroidal anti-inflammatory drugs, may necessitate treatment with colchicine.

Keywords: Gout, hyperuricemia, trauma


How to cite this article:
Dubey RK. Gout as a consequence of bone healing: A diagnostic dilemma. Indian J Pain 2017;31:138-40

How to cite this URL:
Dubey RK. Gout as a consequence of bone healing: A diagnostic dilemma. Indian J Pain [serial online] 2017 [cited 2019 Dec 8];31:138-40. Available from: http://www.indianjpain.org/text.asp?2017/31/2/138/214124


  Introduction Top


Gout is an inflammatory arthritis that is triggered by the deposition of sodium urate crystals within the joints and soft tissues and is frequently associated with hyperuricemia.[1] Hyperuricemia may arise in a wide range of clinical situations that cause overproduction or underexcretion of uric acid, or a combination of both. As uric acid is the ultimate breakdown product of purine nucleotide degradation in humans, any increase in purine production due to accelerated cell turnover may precipitate an acute attack of gout. Acute gout after a bone fracture has not been described in the literature. Here, we report a case of a road traffic accident with a comminuted fracture of the medial condyle of left tibia, which developed acute gout after 10 days of injury.


  Case Report Top


A 42-year-old, nondiabetic, and normotensive male met with a road traffic accident and subsequently had a comminuted fracture of the left tibia involving the medial condyle and the posterior part of the intercondylar region with multiple small and large undisplaced fracture fragments. The fracture line reached up to the attachment of the posterior cruciate ligament (PCL); however, no evidence of discontinuity of PCL was found. There were no significant ligamentous or meniscal injuries either. His body mass index was 25.9 kg/m 2. Three years ago, he was diagnosed to have subclinical primary hypothyroidism (FT4 0.95 ng/dL, FT3 3.0 pg/ml, and thyroid-stimulating hormone 8.45 μIU/ml) and was advised 50 μg of thyroxine sodium per day. Concomitantly, he had raised serum uric acid levels too (7.7 mg/dL); however, no treatment was started as he neither had any symptom of hyperuricemia nor had any history of acute gout in the past.

His leg was immobilized in a long-leg cast for 4 weeks. Oral supplementation of Vitamin D3 and calcium was advised. Ten days after the injury, he woke up in the early morning due to the sudden onset of excruciating pain, redness, and swelling at the base of the left great toe. Over the next few hours, the affected joint became exquisitely tender to the extent that even the weight of bed clothes hurt. The swelling gradually increased, and the overlying skin became tense, warm, dusky red, and inflamed [Figure 1]. Movement of the joint was greatly restricted due to pain. The serum uric acid was 8.6 mg/dL. The thyroid profile was normal. There was no history of recent intake of aspirin, diuretics, cytotoxic drugs, ethanol, or purine-rich diet. A clinical diagnosis of gout was made, and indomethacin 50 mg every 8 h was started. However, the arthritis progressed and there was no pain relief. On the 3rd day, colchicine 0.5 mg was added. Immediately after the first dose of colchicine, the pain decreased significantly. Colchicine was continued at a dose of 0.5 mg every 12 h for three doses. The swelling and pain gradually subsided, and the recovery from arthritis was followed by local desquamation. Four weeks later, allopurinol at a dose of 100 mg/day was started under the guard of colchicine 0.5 mg every 12 h. Colchicine was discontinued after a week. One month after the allopurinol treatment, the serum uric acid level reduced to 5.9 mg/dL.
Figure 1: Acute gouty arthritis of first metatarsophalangeal joint in the fractured lower limb

Click here to view



  Discussion Top


Acute gout, if associated with trauma, essentially presents a diagnostic dilemma. The differential diagnosis consists of cellulitis, septic arthritis, pseudogout, reactive arthritis, psoriatic arthritis, and rheumatoid arthritis. Symptoms of septic arthritis are swelling in joints, fever, and intense pain during movement of the joint. Its presentation may be similar to that of gout; it can occur at any age and does not show any gender predilection. However, a history of intravenous drug abuse or immunosuppression may be present.

Acute gout is primarily a clinical diagnosis. As a manifestation of disturbed purine metabolism, it is often described as one of the most painful conditions experienced by humans.[2] Owing to the lack of uricase enzyme, humans are the only mammals to develop hyperuricemia and gout.[3] Uric acid is a weak acid (pKa 5.8) that, at physiological pH, exists primarily in ionized form in the plasma and the synovial fluid. The amount of urate in the body depends on the balance between production and excretion of uric acid, or often a combination of both the mechanisms. Plasma is saturated with monosodium urate at a concentration of 6.8 mg/dL at 37°C; any further increase in urate concentration increases the risk of supersaturation and crystallization of urate in physiological fluids.[4] Gout has predilection of the metatarsophalangeal joint at the base of the great toe, by virtue of its being a peripheral joint with sluggish blood circulation, low pH, and low temperature.[5]

Bone is a dynamic tissue that consists of metabolically active cells. The healing potential of a fractured bone depends on various biochemical, cellular, hormonal, and pathological mechanisms. Osteoblasts are mature bone-forming cells that secrete osteoid, the unmineralized organic matrix that subsequently undergoes mineralization by inorganic salts (primarily calcium phosphate and calcium carbonate) to provide strength and rigidity to the bone. The metabolism is constantly controlled by a host of calciotropic hormones (parathyroid hormone, Vitamin D, and calcitonin) and local growth factors. Osteoblasts are the sole bone cells that possess parathyroid hormone receptors. The production of 1,25-dihydroxy D3 (biologically active Vitamin D) is regulated by the parathyroid hormone. Vitamin D, apart from its role in bone calcification, has also a much wider role in immunoregulation and cellular differentiation.[6] Hyperparathyroidism and hypothyroidism also impair the excretion of uric acid and may lead to hyperuricemia. Bone healing comprises three discrete but mutually overlapping stages: the early inflammatory stage, the repair stage, and the late remodeling stage. The early inflammatory stage (i.e., first 1–2 weeks) is the most critical phase of bone healing in which inflammation and vascularization occur.

A majority of endogenous overproduction of urate results from increased cell turnover in a variety of proliferative and inflammatory disorders such as trauma, surgery, malignancy, hemolytic anemia, and psoriasis. As the early inflammatory stage of bone healing is also characterized by the increased cell turnover and inflammation, it is likely that acute gout may develop during this stage in certain susceptible individuals. Dunham et al. had observed that the activity of pentose shunt dehydrogenases was very low in the periosteal cells of normal rat metatarsals but increased linearly over the next few days postfracture.[7] The increased activity of dehydrogenase enzymes, thus, leads to elevated levels of D-ribulose-5-phosphate (D-ribulose-5P), the end product of pentose phosphate pathway. D-Ribulose-5P is further converted into D-ribose-5P by the enzyme ribose phosphate isomerase. The enzyme 5′-phosphoribosyl-1-pyrophosphate (PRPP) synthetase catalyzes the synthesis of PRPP from D-ribose-5P and adenosine triphosphate (ATP). The intracellular availability of PRPP is an important factor in the regulation of the rate of de novo purine synthesis in human beings. It has also been observed that the concentration of ATP is increased during the process of bone healing.[8] Degradation of ATP leads to accumulation of adenosine diphosphate and adenosine monophosphate, which can be rapidly degraded to uric acid.[9]

Colchicine, an alkaloid from the plant Colchicum autumnale, is often used in the treatment of gout, familial Mediterranean fever, Paget's disease, and other arthritis. It is a nonselective mitosis inhibitor and, presumably, selectively inhibits the differentiation of osteoblasts. It inhibits both the proliferation and mineralization of bone marrow cells (heterotopic ossification).[10] Prolonged colchicine treatment significantly retards bone healing and fracture union and decreases the bone strength as well. In this particular case, it seems that treatment with colchicine effectively retarded the rapid turnover of cells that precipitated the acute attack of gout, otherwise resistant to indomethacin therapy. In addition, it is also possible that local acidotic conditions, owing to poor blood circulation in the immobilized limb, led to the precipitation of urate crystals in the joints in an otherwise asymptomatic hyperuricemic patient.


  Conclusion Top


The diagnosis of gout in a case of trauma adds to the clinical misperception. Healing of a fractured bone, through multiple mechanisms, can precipitate acute gout, particularly in the presence of certain predisposing factors such as hypothyroidism, preexisting hyperuricemia, or tissue hypoxia. Acute inflammation and pain, if resistant to nonsteroidal anti-inflammatory drugs, may necessitate treatment with colchicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Choi HK, Mount DB, Reginato AM; American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med 2005;143:499-516.  Back to cited text no. 1
[PUBMED]    
2.
Johnson RJ, Rideout BA. Uric acid and diet – Insights into the epidemic of cardiovascular disease. N Engl J Med 2004;350:1071-3.  Back to cited text no. 2
[PUBMED]    
3.
Wu XW, Muzny DM, Lee CC, Caskey CT. Two independent mutational events in the loss of urate oxidase during hominoid evolution. J Mol Evol 1992;34:78-84.  Back to cited text no. 3
[PUBMED]    
4.
Lin KC, Lin HY, Chou P. The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol 2000;27:1501-5.  Back to cited text no. 4
[PUBMED]    
5.
Simkin PA, Pizzorno JE. Transynovial exchange of small molecules in normal human subjects. J Appl Physiol 1974;36:581-7.  Back to cited text no. 5
[PUBMED]    
6.
Reichel H, Koeffler HP, Norman AW. The role of the Vitamin D endocrine system in health and disease. N Engl J Med 1989;320:980-91.  Back to cited text no. 6
[PUBMED]    
7.
Dunham J, Shedden RG, Catterall A, Bitensky L, Chayen J. Pentose-shunt oxidation in the periosteal cells in healing fractures. Calcif Tissue Res 1977;23:77-81.  Back to cited text no. 7
[PUBMED]    
8.
Buchholz J, Huber FX, Meeder PJ, Muhr G, Kreitz GK, Herzog L. Detection of high-energy phosphates in cortical bone as an indicator of bone healing and remodelling: Use of a rabbit model. J Orthop Surg (Hong Kong) 2004;12:205-9.  Back to cited text no. 8
[PUBMED]    
9.
Puig JG, Fox IH. Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate. J Clin Invest 1984;74:936-41.  Back to cited text no. 9
[PUBMED]    
10.
Salai M, Segal E, Cohen I, Dudkiewicz I, Farzame N, Pitaru S, et al. The inhibitory effects of colchicine on cell proliferation and mineralisation in culture. J Bone Joint Surg Br 2001;83:912-5.  Back to cited text no. 10
[PUBMED]    


    Figures

  [Figure 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed3841    
    Printed36    
    Emailed0    
    PDF Downloaded108    
    Comments [Add]    

Recommend this journal