02 November 2023: Articles
Redefining Foot Symptoms in a Kidney-Pancreas-Transplanted Type 1 Diabetic Patient: Challenging the Conventional Charcot Foot Diagnosis
Unusual clinical course, Challenging differential diagnosisPlator Memaj1ABCDEF, Jorge César Correia 1ABCDEF, Marie Davat2DE, Domizio Suva2DE, Karim Gariani1ABCDEF*
Am J Case Rep 2023; 24:e939071
BACKGROUND: Acute Charcot foot can be difficult to diagnose, especially because of other alternate diagnoses that can mimic this condition, particularly stress fracture and acute bone and joint infections, which are 2 conditions that require immediate management. Here, we present the case of a patient who received kidney-pancreas-transplantation for type 1 diabetes mellitus, who consulted for right foot pain after walking.
CASE REPORT: Our patient was a 47-year-old man who had benefited from a kidney-pancreas transplantation in 2014 for type 1 diabetes and terminal kidney failure and was recently followed for a right foot plantar ulcer that was fully healed. He later presented for right foot pain after walking. Clinical examination showed a red, swollen, and warm foot. Blood test results were unremarkable. Imaging (X-ray/MRI) revealed features compatible with acute Charcot foot. The management consisted of prompt right-foot offloading followed by physiotherapy and adapted orthopedic insoles.
CONCLUSIONS: This case shows the successful treatment of an active phase of Charcot foot, which avoided the classic transition to chronic Charcot foot with severe osteoarticular destruction. Arguments were developed to rule out other possible diagnoses. The underlying mechanisms of Charcot foot in diabetic patients are related to the neurological and micro-vascular complications induced by poor glycemic control, but the mechanisms are unclear. This case report may help clinicians to better understand and consider another less known and less frequent diagnosis when faced with these clinical features.
Keywords: Diabetes Complications, Diabetes Mellitus, Diabetic Foot
Both type 1 and type 2 diabetes mellitus (DM) can have several chronic complications that are especially common in patients with poor glycemic control. One of these complications, known as diabetic foot, is the consequence of nerve damage (peripheral neuropathy), along with poor blood flow (peripheral vascular disease) [1,2]. This leads to loss of the protective sensation in the feet and increased risk of chronic non-healing wounds with higher risk of infection. Neurogenic arthropathy, also called Charcot arthropathy, is the destruction of osteoarticular structures of the feet that develops on the background of diabetic neuropathy . Furthermore, DM in general is known to increase bone fragility and risk of fracture through different mechanisms depending on the type of diabetes . We present here the case of an unusual presentation of a stress fracture that initially was considered and treated as a neuropathic arthropathy (“Charcot foot”). Considering that the patient was recently followed for a right foot ulcer, an underlying infection was sought and excluded. Finally, after further investigations, the retained diagnosis was a stress fracture of the head of the fourth metatarsal bone, the cuboid bone, and the intermediate cuneiform bone due to bone insufficiency.
Our patient was a 47-year-old man from Eastern Europe, known to have type 1 diabetes mellitus (T1DM) since the age of 22 years, who had a kidney–pancreas transplant at age 40 years, followed by another pancreas transplant 4 years later due to graft necrosis 3 years after the first transplant. This second transplant was successful and since then he has been insulin independent with good glucose control as shown by 4.9% glycated hemoglobin. The patient was therefore considered cured from T1D after suffering from it for 18 years. Anti-rejection treatment consisted of daily per os prednisone and per os tacrolimus, which were taken cautiously by the patient for 7 years.
The patient was known to have severe peripheral polyneuropathy without lower-extremity arterial disease. Prior to the current episode, he had been treated a few months before at the diabetic foot outpatient clinic for a plantar ulcer on the head of the fifth metatarsal of the right foot, which was fully healed.
He returned to the diabetic foot clinic for a new pain when walking, localized on the dorsal side of the right foot, that had been evolving for 1 week. There was no trauma reported or new wound. The patient noted a new swelling, accompanied by redness, which prompted the consultation. He had no other concerns and had no recent history of strenuous physical activity such as running, jumping, hiking, exercising, or any other physical event. At this time the differential diagnosis was relatively broad and included Charcot foot, cellulitis, deep vein thrombosis, fracture, and gout.
Upon physical examination, the patient had no fever. The right foot was swollen, red, and warm, with pain on palpation of the Lisfranc ligament (Figure 1). Paresthesia measured with a tuning fork was severely reduced at 2/8 on both hallux, 3/8 on the right malleolus, and 0/8 on the left malleolus. The rest of the neurological status of the lower limbs was normal, notably strength, superficial sensitivity, and deep sensitivity. Blood tests were performed and results were unremarkable, notably no inflammatory syndrome. An X-ray of the right foot showed no bone lesion (Figure 2). In view of the significant pain and high suspicion of Charcot foot, the patient was hospitalized in the orthopedic unit.
A foot MRI was performed, which showed a typical image of a subchondral fracture of the head of the fourth metatarsal bone, the cuboid bone, and the intermediate cuneiform bone with hypo-signal in T1, hyper-signal on the T2 and T2 FS sequences, and associated edema of the metatarsal, suggestive of a stress fracture (Figure 3). Overall, the clinical and radiological picture was strongly in favor of Charcot foot, which was the diagnosis retained.
The treatment consisted of toe touch bearing with a rigid insole and crutches, without immobilization of the foot. The patient was hospitalized for 5 days. He received subcutaneous 40 mg daily as thromboprophylaxis. The patient used the insole and the crutches during and after the hospitalization for 38 days in total with adaptation of the orthopedic insoles to avoid hyper-pressure with no painkiller needed.
After a 5-day hospital stay, the patient was sent home and had to continue walking with crutches and toe touch bearing. He was seen weekly, with full recovery by week 5. The pain has completely resolved, and the radiographs (week 2 and 5) were reassuring. The thromboprophylaxis was maintained until full weight bearing. The patient was fully discharged after 2 months of ambulatory follow-up.
Bone mineral density has been found to be low in people with T1DM , leading to increased bone fragility and increased risk of developing fractures associated with significant morbidity . The prevention of bone damage remains a major challenge, both for the quality of life of patients and for the costs generated by it .
In recent years, there has been increased attention to bone fragility in patients with T1DM, who have an especially high rate of bone fractures. The risk of developing a femoral neck fracture is 6–7 times greater in patients with T1DM than in non-diabetic individuals . In addition, other studies have shown a general increase in all types of bone fracture, with a risk 3 times greater in patients with T1DM (1.8 times higher in men and 4.1 times higher in women) . Although T1DM appears to be associated with an increased risk of bone fracture, the underlying pathophysiology leading to bone fragility appears to be different than in T2DM. One of the mechanisms that could explain this association may be altered bone remodeling, and blood markers of bone resorption (CTX) and bone formation (osteocalcin) are lower in T1DM patients who also have vitamin D deficiency. The insulinopenia found in T1DM patients seems to contribute to bone fragility since insulin is a hormone having an anabolic action on bone .
Bone loss and fracture are also recurrent complications in patients who have received a solid organ transplant. It is estimated that bone fractures occur in 45–49% of patients who have undergone simultaneous kidney-pancreas transplantation within 2 years after the transplant . The different mechanisms explaining this link are multiple and complex. Immunosuppressive drugs such as corticosteroids and calcineurin inhibitors play a significant role in weakening bones. Other factors, such as advanced age, pre-existing diabetes, history of long-term chronic renal failure before transplantation, history of bone fracture, and female sex, play an important role in bone fragility .
One study showed a significant difference in fracture risk between kidney transplant patients and kidney–pancreas transplant patients, with a reduced risk in the latter group. Indeed, fractures are found in 5.9% of single-kidney transplant patients and in 4.7% of kidney–pancreas transplant patients . The risk of bone fracture over a period of 5 years after transplantation in the kidney–pancreas transplant patients is 31% lower than in kidney transplant recipients. The sites most affected by fractures are the femur (25% of fractures), ankle (16% of fractures), and tibia (13% of fractures) .
The main differential diagnosis of bone stress fracture in diabetic patients is Charcot foot, which must be promptly excluded when suspected. The pathogenesis of foot is the result of a sensory neuropathy favoring the occurrence of micro-trauma associated with neurovascular damage increasing blood per-fusion favoring local inflammation . Charcot foot is a serious condition that has a major impact on the lives of diabetic patients. Indeed, a study has shown that life expectancy of patients who have developed Charcot foot is 14.4 years shorter than in the general population .
Charcot foot has an incidence rate of less than 1% in the general diabetic population . The incidence rate of peripheral neuropathy in the same population is 9–32% . Patients with severe peripheral polyneuropathy have a higher risk of developing Charcot foot, with an estimated prevalence of 13% . However, this condition may be underestimated because it is difficult to diagnose. Several retrospective studies have shown a link between solid organ transplantation and the development of Charcot arthropathy, with an increase in the incidence of Charcot neuroarthropathy in patients who have benefited from kidney–pancreas transplant or kidney-only transplant .
A study that assessed the rate of patients developing Charcot arthropathy after transplantation (kidney–pancreas and kidney) with post-transplantation follow-up of more than 2 years found that 14.8% of these patients presented with Charcot foot and all these patients had peripheral neuropathy. There was a statistically significant difference between kidney–pancreas transplant patients (18.4%) and single-kidney transplant patients (11%) .
The initial differential diagnosis mainly includes stress fracture, bone and/or joint infection, and Charcot foot. In our patient, several elements were against a stress fracture, namely the absence of trauma related to a sport or an overload of the bone, the absence of significant pain, and the lack of pathological radiological signs. Moreover, in the event of a stress fracture, the presence of peripheral neuropathy is not typical and the bone consolidation time is generally longer than 38 days. The clinical elements suggesting lack of a bone or joint infection were the absence of an acute or chronic wound, the absence of biological signs of infection, and radiological images showing areas of bone lysis resembling Charcot foot, not in the acute phase but only in the chronic phase, which was not the case here.
Our patient had many features suggestive of acute Charcot foot, namely: onset in a neuropathic foot, absence of pain, normal X-ray at the beginning with abnormal MRI, intraosseous edema on several bones of the foot plus fissures then fractures depending on the time of the MRI, multiple bone involvement, no wound in front of the affected bone, clinical appearance similar to a soft-tissue infection but without biological signs, and rapid consolidation when managed by rapid discharge from the hospital at the stage when the radiograph is still normal (stage 0 of the modified Eichenholtz radiological classification).
It is necessary to insist on the clinical aspect, the MRI, and the rapid discharge without waiting for the results of the MRI, which allows us to envisage not seeing chronic Charcot feet diagnosed and treated too late.
In management of acute Charcot foot, the offloading mode is controversial between non-removable cast, removable boot, or orthopedic insoles in high shoes. Rapid discharge from the hospital without waiting for MRI results can be a mistake and can contribute to delayed treatment and chronic disease. The authorization of support is also controversial and can include support forbidden (especially if fractures are proven on the X-ray), or support protected by canes and walker boot or cast. The duration of immobilization is based on <2°C drop in local foot temperature compared to the healthy foot .
Our patient had a rapid diagnosis of Charcot foot in the acute phase, which is rare, and was discharged at the pre-fracture stage and thus consolidated, avoiding the osteoarticular dislocation, which is common in patients with Charcot foot. Clinicians should have a high index of suspicion of acute Charcot foot in patients who were formerly diabetic and were transplanted (kidney–pancreas or kidney-only) present with a swollen and red foot in the context of peripheral polyneuropathy, and an MRI of the foot must be performed to make the definitive diagnosis.
The diagnosis retained in this case was an early acute neuropathic arthropathy (“Charcot foot”). Charcot foot in the acute phase should be considered in any diabetic patient with neuropathy who has a foot that has increased in volume with redness and warmth (>2°C compared to the normal foot) associated with moderate foot pain, even with pancreas transplantation, and especially with corticosteroid therapy and in the absence of an ulcer. Such patients should immediately cease bearing weight on the affected foot and have an MRI even if the X-ray is normal.
FiguresFigure 1.. Clinical presentation. Picture of the patient’s feet put next to each other to show the swollen red right foot compared to the healthy left foot. Figure 2.. Right foot radiography. Sagittal incidence, where we can see vascular calcifications along with talonavicular osteoarthritis with no suggestion of Charcot foot. Figure 3.. (A-C) MRI of the right foot with different incidences showing multiple fractures (see text) with associated mechanical overload bone edema typical of a bone stress fracture.
1.. Bandyk DF, The diabetic foot: Pathophysiology, evaluation, and treatment: Semin Vasc Surg, 2018; 31(2–4); 43-48
2.. Volmer-Thole M, Lobmann R, Neuropathy and diabetic foot syndrome: Int J Mol Sci, 2016; 17(6); 917
3.. Trieb K, The Charcot foot: Pathophysiology, diagnosis and classification: Bone Joint J, 2016; 98-B(9); 1155-59
4.. Starup-Linde J, Hygum K, Harsløf T, Langdahl B, Type 1 diabetes and bone fragility: Links and risks: Diabetes Metab Syndr Obes, 2019; 12; 2539-47
5.. Moseley KF, Type 2 diabetes and bone fractures: Curr Opin Endocrinol Diabetes Obes, 2012; 19(2); 128-35
6.. Napoli N, Chandran M, Pierroz DD, Mechanisms of diabetes mellitus-induced bone fragility: Nat Rev Endocrinol, 2017; 13(4); 208-19
7.. Rakel A, Sheehy O, Rahme E, Lelorier J, Does diabetes increase the risk for fractures after solid organ transplantation? A nested case-control study: J Bone Miner Res, 2007; 22(12); 1878-84
8.. Nikkel LE, Iyer SP, Mohan S, Pancreas–kidney transplantation is associated with reduced fracture risk compared with kidney-alone transplantation in men with type 1 diabetes: Kidney Int, 2013; 83(3); 471-78
9.. van Baal J, Hubbard R, Game F, Jeffcoate W, Mortality associated with acute Charcot foot and neuropathic foot ulceration: Diabetes Care, 2010; 33(5); 1086-89
10.. Anthony ML, Cravey KS, Atway SA, Development of Charcot neuroarthropathy in diabetic patients who received kidney or kidney-pancreas transplants: J Foot Ankle Surg, 2019; 58(3); 475-79
11.. Mautone M, Naidoo P, Zhou K, Imaging of the spectrum of bony injuries in the diabetic foot: A case series with emphasis on non-Charcot fractures: BJR Case Rep, 2017; 3(4); 20170026
01 Dec 2023 : Case reportLife-Threatening Electrical Storm Following Liver Transplantation: A Case Report
Am J Case Rep In Press; DOI:
01 Dec 2023 : Case reportInnovative Approach to Difficult Airway Management: Utilizing the Cook® Airway Exchange Catheter for Double...
Am J Case Rep In Press; DOI:
01 Dec 2023 : Case reportSuccessful Conservative Therapy for Infected Penile Implants: A Case Series
Am J Case Rep In Press; DOI:
Most Viewed Current Articles
06 Dec 2021 : Case reportLipedema Can Be Treated Non-Surgically: A Report of 5 Cases
Am J Case Rep 2021; 22:e934406
07 Dec 2021 : Case reportEdwardsiella tarda: A Classic Presentation of a Rare Fatal Infection, with Possible New Background Risk Fac...
Am J Case Rep 2021; 22:e934347
19 Jul 2022 : Case reportAtlantoaxial Subluxation Secondary to SARS-CoV-2 Infection: A Rare Orthopedic Complication from COVID-19
Am J Case Rep 2022; 23:e936128