Description of the condition
Osteoarthritis (OA) is defined as a failure of one or more synovial joints (Felson 2012). It is a condition in which all the structures of the joint have undergone pathological change, often in concert. Its cardinal features are: focal loss of articular cartilage, proliferation of new bone and remodelling of the joint contour (Doherty 2010).
OA preferentially targets certain large and small joints, while sparing others. The knee and hip are the principal large joints involved (Doherty 2010).
OA is the most common disease of joints in adults around the world (Felson 1988). In the United States, OA is the most frequent cause of disability among adults, and the fourth most common cause of hospitalisation (Murphy 2012). OA is the leading indication for joint replacement surgery in high-income countries; 905,000 knee and hip replacements were performed in the United States in 2009, at a cost of $42.3 billion (Murphy 2012). Between 2005 and 2010 the number of total hip arthroplasties in the United Kingdom increased by 16% (Pivec 2012).
OA is uncommon in adults aged less than 40 years and highly prevalent in those aged over 60 years (Felson 2012). OA affects 10% to 25% of people aged over 65 years (Doherty 2010). Women aged over 55 years experience OA more commonly than men of equivalent age (Shipley 2009), and this gender differential increases with advancing age (Felson 2012). Different racial groups are affected differently: hip OA, for example, is more common in Europeans than in Asians, but knee OA less common (Shipley 2009).
The characteristic symptoms of OA are joint pain, joint ‘gelling’ (i.e. stiffening and pain after any period of immobility), joint instability and loss of function. The characteristic signs are joint tenderness, crepitus (i.e. a crackling or grating feeling or sound) on movement, limitation of range of movement, joint effusion, bony swelling, and wasting of muscles (Shipley 2009).
The joint pain of OA is typically activity-related. It comes on during or just after joint use (e.g. hip pain when climbing stairs), then gradually subsides. Early in the disease course, the pain of OA is episodic and self-limiting. With advancing disease, however, the pain becomes continuous, and may be troublesome even at night (Felson 2012).
Inflammation is not usually a prominent clinical feature of OA (Doherty 2010).
The diagnosis of OA is based on a history of joint pain worsened by movement (Sinusas 2012). Plain radiography often helps in confirming the diagnosis, but laboratory testing usually does not.
The American College of Rheumatology (ACR) has developed diagnostic criteria for the presence of OA based on clinical criteria alone (for hand OA), and on clinical, laboratory and radiographic criteria (for hip and knee OA) (Brion 2010). The diagnostic criteria for knee OA are the most complex, and have recently been validated using arthroscopically-defined cartilage damage scores (Wu 2005). The ACR diagnostic criteria are summarised in Appendix 1, Appendix 2 and Appendix 3.
Interventions to treat OA have been assessed in previous Cochrane reviews and the number of effective treatment options is limited, as shown below:
Total joint replacement of the hip, knee, or shoulder is currently recommended for patients who have persistent severe OA pain and disability, despite maximal medical therapy (Sinusas 2012).
Description of the intervention
‘Leech’ is derived from the Old English word laece, meaning physician (Porshinsky 2011).
Leeches have been used extensively for the past half-century in plastic, reconstructive and trauma surgery (Derganc 1960; Porshinsky 2011). In the 1980s French microsurgeons began using leeches to assist with distal digital replantation involving arterial repairs only (Foucher 1981).
The use of leeches for phlebotomy (i.e. bloodletting), and for specific therapeutic indications, dates back to ancient Egypt (Whitaker 2012). Leeching, or hirudotherapy, was popular in Western society until the First World War, when supplies of wild leeches could no longer be guaranteed from the usual sources in Eastern Europe. There has, however, been a steady resurgence from the 1970s onwards, associated with the commercial farming of leeches (Koeppen 2013). In Germany alone, approximately 100,000 therapeutic leech sessions take place each year, corresponding to around 350,000 leeches used annually (Koeppen 2013).
Leeches belong to the phylum Annelida (i.e. segmented invertebrate worms), class Hirudinea. An accepted high-level leech taxonomy is given at Appendix 4. Medicinal leeches all fall under the family Hirudinidae. The important biological characteristics of leeches are listed in Appendix 5.
Three leech species, Hirudo medicinalis, Hirudo verbena and Hirudo orientalis, have been widely used in Europe as therapy. There is currently some debate as to whether these are three reproductively isolated biospecies, or whether they are in fact a complex of closely related and potentially interbreeding species (Kutschera 2012).
Other leech species that have been regularly used in therapy include Macrobdella decora (the American medicinal leech), Hirudinaria granulosa (the Indian medicinal leech), Hirudo michaelseni and Hirudo nipponia, (Zaidi 2011).
Leech therapy involves (Yantis 2009):
an initial leech bite, which is usually painless;
an attachment period lasting from 20 to 45 minutes, during which the leech typically sucks between 5 and 15 mL of blood; and
a post-attachment period, during which the wound may continue to bleed, for some hours.
Clear fluid flows copiously from the skin of the leech as it feeds (Worth 1951). After feeding, the tripartite jaw of the leech leaves a 0.3 cm diameter three-pronged bite wound on the host’s skin, sometimes referred to as the ‘Mercedes-Benz sign’. After the post-attachment period, the wound scabs over and the resulting scar quickly shrinks in size and becomes pale; within a few months it is indiscernible (Michalsen 2007).
Effectiveness of the intervention – empirical evidence
There is empirical evidence, based on contemporary clinical experience in numerous countries and also on published and unpublished non-randomised studies, that leeches may be effective therapy for a wide range of medical disorders. Leeches seem to be effective in four broad disease categories, as follows (Michalsen 2007):
Pain syndromes. Benefits from leech therapy have been reported in cancer pain (Kalender 2010), cervical spine syndrome (‘whiplash injury’), cervicobrachialgia, chronic low back pain/lumbago, iliosacral joint pain and migraine (Hyson 2005), osteoarthritis (ankle, hip, knee, shoulder, small joint), and sports injuries (Deuser 1971).
Inflammatory states. Benefits have been reported in abscesses associated with inflammation, acute gout (Panda 2012), inflammatory diseases of internal organs (as adjuvant therapy only), paronychia (Graham 1995), parotitis and sialadenitis (i.e. chronic inflammatory and dystrophic disease of the salivary glands) (Singh 2009), rheumatic disease (rheumatoid arthritis, fibromyalgia), systemic lupus erythematosus (Cheng 2005), tendinitis, and tendovaginitis (i.e. lateral epicondylitis).
Circulatory disorders. Benefits have been reported in acute superficial phlebitis, arterial hypertension, chronic venous insufficiency, frostbite (Munshi 2005), haematoma (including acute macroglossia, sublingual haematoma and periorbital haematoma) (Porshinsky 2011; Panda 2012), haemorrhoids, ocular circulation disorders, peripheral circulation disorders (including peripheral occlusive arterial disease), priapism, spider naevi, and varicose veins (RCT evidence from Nigar 2011). Leeches also seem to be effective in treating the circulatory complications of diabetes mellitus (Abdualkader 2013).
Other conditions. Benefits have been reported in dental pathology (alveolar abscess, oral pemphigus, periodontitis) (Srivastava 2010), herpes zoster, otitis media, otitis externa, ovarian cysts (Hyson 2005), and tinnitus (Michalsen 2007). Leeches may be of benefit in some neurological disorders, such as epilepsy (Sun 2007).
Safety of the intervention – empirical evidence
Leeches are contraindicated in pregnancy, in infants and in patients with chronic gastrointestinal and other bleeding disorders. They should not be used in patients taking anticoagulant medication, or in patients with anaemia, haemophilia, known protein allergies, or serious organic disease with immunosuppression (including HIV infection) (Michalsen 2007). For cosmetic reasons, leeches should not be used in patients with a tendency to keloid scar formation (Michalsen 2007).
Provided the above precautions are observed, the therapeutic use of leeches appears to be safe. Systemic infections and septicaemias due to Aeromonas spp bacteria, which are naturally present in the digestive tract of leeches (Appendix 5), have been described only in the context of reconstructive and trauma surgery, and in patients who were severely injured or otherwise acutely ill (Whitaker 2012). The infection risk from the use of leeches in non-traumatised patients is considered to be minimal (Lent 1986), and with careful selection and preparation of the leeches it may be as low as zero per cent (de Chalain 1996).
After many years of demonstrably safe clinical use, Hirudo medicinalis received official approval as a medical device in 1984 from the USA’s Food and Drug Administration (Rados 2004).
How the intervention might work
The principal mechanism of action in leech therapy appears to be the secretion of a complex mixture of biologically active substances from the salivary glands of the leech at the time of biting, and the injection of these active substances into the animal host (Singh 2009). The exact composition and relative mix of the secreted bioactive substances varies between leech species (Sawyer 1986), and many substances have not yet been identified. The active substances include (Singh 2009):
Anaesthetic and analgesic compounds. A specific analgesic within leech saliva is yet to be identified (Koeppen 2013).
Anticoagulant, thrombolytic and vasodilatory agents. These include antiplatelet agents and factor Xa inhibitors (Abdualkader 2013). All leeches appear to secrete hirudin, a potent anticoagulant which was first demonstrated in leech saliva by the English physiologist, John Haycraft (Haycraft 1884); the synthetic analogues desirudin and lepirudin have recently been approved by the FDA (Abdualkader 2013).
Other substances. Bactericidal and bacteriostatic agents.
Why it is important to do this review
OA is a painful chronic disease, and a major influence on a patient’s quality of life.
Because of its high global prevalence, especially in the elderly, OA is now a leading worldwide cause of disability (Felson 2012). This global prevalence is increasing – both due to the progressive ageing of Western societies and because of increasing obesity, a major risk factor for OA (Felson 2012). In the United States, OA prevalence will increase by 66% to 100% by 2020 (Felson 2012).
Current treatment regimens for OA are sub-optimal. There is an urgent need for agents to halt or reverse OA, but no such products exist (Shipley 2009). While acetaminophen and topical analgesics appear safe in OA, the safety profile of oral NSAIDs and of opiates is poor (Reid 2012). Most drug therapies provide mild to moderate pain relief only. Their long-term safety and long-term efficacy are undetermined, as are their effects in diverse populations (e.g. adults aged over 65 years) (Reid 2012). There are professional concerns around the long-term safety of metal-on-metal arthroplasties (Pivec 2012).
An inexpensive, effective, low-risk, non-pharmacological intervention would constitute a significant advance in OA treatment.