Introduction
Neuropathic osteoarthropathy, called Charcot disease after a French neurologist, Jean-Martin Charcot (1825–1893), is a rapidly progressing complication of nerve fiber damage manifested by destruction of osseous and articular structures of the foot and ankle joint. At present, the main cause of the disease worldwide is diabetic polyneuropathy. Regions with endemic leprosy, which causes nerve fiber degeneration, are an exception. The disease can also be caused by: spinal cord and peripheral nerve injury, syphilis, congenital central nervous system defects, neurodegenerative diseases, such as neuropathy in the course of amyloidosis, vitamin deficiency, alcoholism or heavy metal poisoning(1). The clinical picture is characterized by considerable edema, redness and increased skin temperature of the foot and ankle with relatively slight pain sensation. Charcot arthropathy may mimic infectious arthritis, a gout attack, autoimmune inflammation, injury or deep vein thrombosis. An ultrasound scan may be the initial examination ordered in patients presenting with such symptoms. In this situation, a diagnostician familiar with such a pathology can help establish the correct diagnosis and implement appropriate therapy.
Case presentation
A forty-eight-year-old man with type 1 diabetes mellitus diagnosed at the age of 13 and arterial hypertension was admitted to the Clinic of Rheumatology due to edema and pain in the left foot that had intensified gradually for four months considerably restricting mobility. The referring physician suspected rheumatoid arthritis or a gout attack. The interview revealed the history of ankle sprain injury sustained four months before. On physical examination, the patient was in a good condition with considerable edema, redness and increased temperature of the left foot. There were no fever, wounds or purulent changes in the area (Fig. 1). In laboratory tests, inflammatory markers and uric acid levels were normal. Rheumatoid factor and anti-citrullinated protein antibodies were negative. Daily glucose levels exceeded the upper limit considerably (max. 350 mg%) despite intensive insulin therapy. The level of glycated hemoglobin amounted to 9.2 mg%. Doppler sonography of the lower extremities ruled out thrombosis.
Fig. 1
Clinical picture of the left foot with Charcot arthropathy

An utrasound examination showed the following: an inflammatory reaction and degeneration in the 1st–4th metatarsophalangeal and tarsometatarsal articulations with erosions and destruction of bone epiphyses, synovial thickening with hypervascularization, uneven metatarsal outline with edema, thickening and periosteal hyperemia (inflammatory reaction) (Fig. 2).
Fig. 2
US imaging of the left feet: inflammatory and destructive changes in the 2nd metatarsophalangeal joint with erosions, synovial thickening with signs of hypervascularization (A,B), uneven periosteum of the 2nd metatarsal with intense blood flow (C)

Radiography of the left foot (Fig. 3) revealed destructive osteolytic changes within the bones at the 2nd–4th metatarsophalangeal joints with detached bony fragments, geodes in the head of the 5th metatarsal, bases of certain metatarsals and head of the proximal phalanx of the 5th digit. Moreover, the examination showed osteosclerotic remodeling of the proximal phalanx of the 2nd digit and 1st–3rd metatarsal shafts as well as periosteal buildup in the 2nd–5th metatarsals and proximal phalanges of the 2nd and 3rd digits.
Fig. 3
X-ray of the feet. A. AP; B. oblique X-ray of the left foot: destructive osteolytic changes within the bones composing the 2nd–4th metatarsophalangeal articulations with detached bony fragments, geodes in the head of the 5th metatarsal, osteoclast remodeling of the proximal phalanx of the 2nd digit and 1st–3rd metatarsal shafts as well as 5th metatarsal (to a lower extent) as well as periosteal buildup in the 2nd–5th metatarsal shafts and proximal phalanxes of the 2nd and 3rd digits. Typical image of diabetic osteoarthropathy

Based on the imaging findings, Charcot arthropathy was diagnosed.
The patient was consulted by a neurologist, orthopedist, ophthalmologist and diabetologist. The neurological examination showed features typical of diabetic polyneuropathy – abnormal sensation of pain, touch, vibration and placement with normal temperature sensation. The ophthalmologic examination confirmed simple retinopathy. The orthopedist recommended resting the foot, everyday foot hygiene and more intensive treatment of diabetes. The diabetologist from the Diabetic Foot Clinic recommended as follows: resting the foot combined with muscle exercises and electromagnetic field therapy for six weeks, a semi-rigid cast or Walker orthosis, a radiological check-up after three months, calcium and vitamin D supplementation, possible bisphosphonate treatment depending on the result of densitometry (lumbar spine T-score was –2.5) and more intensive treatment of diabetes with an insulin pump.
Discussion
Neuropathic osteoarthropathy is a relatively rare complication of diabetes that can have severe consequences. It is believed that approximately 28% of patients with insulin-dependent diabetes mellitus develop polyneuropathy whilst Charcot disease is observed in only 1% of patients with polyneuropathy(2). By contrast with individuals with type 2 diabetes, patients with type 1 diabetes are more susceptible to this complication. Injury, osteitis and surgery within the foot can be triggering factors.
Peripheral nerve injury results in pain sensation disorders and repeated microinjuries which lead to microfractures as well as bone and articular structure degeneration. Due to proprioceptor damage, the foot becomes susceptible to repeated and undiagnosed injuries. Sympathetic denervation probably results in disorders in the autonomic regulation of smooth muscle tension in arterioles, thereby leading to increased blood flow to the bones and the initiation of a local inflammatory reaction (this would explain edema and skin redness in initial stages). It seems that osteoclasts formed from migrating monocytes play a crucial role in this process. Proinflammatory cytokines, such as IL-6, IL-1 and TNF-α, as well as activation of receptor activator for nuclear factor κ B ligand (RANKL) contribute to the differentiation of mature osteoclasts from precursor cells. The consequences are abnormal bone turnover and locally decreased bone density. Besides, it is believed that local inflammation is intensified by neuropeptide deficiencies, e.g. nitric oxide or substance P(3).
Examinations that can detect the earliest signs include scintigraphy, which shows changes in the form of increased tracer uptake, and magnetic resonance imaging (MRI) in which one can observe soft tissue swelling, bone marrow edema, joint effusion as well as synovial and bone marrow signal increase upon contrast agent administration (Fig. 4). Radiographic images are initially normal. When taken with time intervals, however, they show subluxation, luxation, pathological fractures and bony debris, which altogether make up a typical image of bone destruction(4). In our patient, the inflammatory process was probably triggered by the injury sustained six months before. The radiographs showed already fixed destructive and osteolytic changes, bone fragmentation and osteoclast remodeling, which attests to the advancement of the process and irreversibility of the changes.
Fig. 4
A. Scintigraphy of the feet with the use of 99mTc-sulesomab-labelled leukocytes: a focus of intense tracer accumulation within the navicular bone. B. AP scintigraphy of the feet shows a hot spot corresponding to sclerosis and fracture – an initial stage of Charcot neuroarthropathy, probably triggered by infection

Patients with edema, redness and pain in the foot are frequently first referred to an ultrasound examination. Ultrasound imaging enables assessment of soft tissues and posttraumatic changes earlier than radiography. In the case presented above, the image, particularly periosteal buildup along metatarsal shafts with soft tissue inflammation and advanced destructive changes, was typical of a diabetic foot.
Conclusion
The most common cause of Charcot arthropathy is polyneuropathy in the course of diabetes mellitus. The disease affects the foot and ankle joint. The clinical picture, i.e. edema, redness and increased skin temperature, mimics other conditions, such as a gout attack, infectious or autoimmune arthritis, injury or deep vein thrombosis. Ultrasound imaging is not the examination of the first choice when the disease is suspected. However, clinicians frequently misinterpret the symptoms and refer patients for ultrasound examination. An experienced ultrasonographer who is familiar with possible complications of diabetes and knows the image of Charcot arthropathy can arrive at a correct diagnosis thus accelerating further diagnostic workup and therapy(5).
Conflict of interests
The authors report no conflict of interests.