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12 Articles in Volume 16, Issue #10
2016 Practical Clinical Advances: Ketamine and Metformin
Case Challenge: Amniotic Allograft Reduces Joint and Soft Tissue Pain
Challenges of Treating Young Patients With a Terminal Prognosis
Defining Palliative Care
Discussing Benefits of Palliative Care
Evaluation of Antiemetic Pharmacotherapy in the Setting of Opioid Withdrawal
Fibromyalgia, Chronic Fatigue, and Chronic Fatigue Syndrome
Gabapentin Dosing for Neuropathic Pain
IV Acetaminophen Reduces Need for Opioids in Burn Patients
Opioid-Induced Constipation: New and Emerging Therapies—Update 2016
Osteopathic Treatment Considerations For Head, Neck, and Facial Pain
Tips From the Field: Deconstructing the Art of Headache Medicine

Case Challenge: Amniotic Allograft Reduces Joint and Soft Tissue Pain

Two case presentations demonstrate the use of injectable micronized dehydrated amniotic/chorionic membrane allograft (mDHACM) to help reduce pain and enhance healing for patients with foot and ankle pain.

Foot pain is one of the most common orthopedic complaints; it affects more than 1 million people per year.1 The diagnosis of foot pain is based on the patient’s symptoms, which are characterized by classic signs of inflammation—pain, swelling, and loss of function.1

Foot pain can be caused by repeated trauma or overuse that creates microtears in the affected joint, concurrently damaging the immediate surrounding soft tissue.2,3 Additional diagnostic modalities, including  musculoskeletal ultrasound, computerized tomography (CT) scans, magnetic resonance imaging (MRI), and electromyography (EMG) studies may be used to rule out related pathologies.

An injection containing AmnioFix is being prepared. Photo courtesy of Mimed Group Inc.

Common treatment options available for foot pain include rest, stretching exercises, orthotics, cryotherapy, oral analgesics, corticosteroid injections, phonophoresis, and local injections of platelet-rich plasma.4-6 No single treatment is guaranteed to relieve pain.7 Traditional nonoperative management can lead to a temporary abatement of symptoms—during which the degenerative process related to repetitive microtearing and inflammation continues to occur.2,3,6,8

A recent study has shown that locally injected amniotic-derived mesenchymal cells aid in the recovery of injured peripheral nerves.9 A treatment that reduces inflammation of soft tissues and nerves, and that allows for rapid return to pain-free activities is highly desirable and the basis for the use of dehydrated micronized amnion/chorion.  

The purpose of this case review is to present injectable micronized dehydrated amniotic/chorionic membrane (mDHACM; AmnioFix Injectable, Mimed Group Inc, Marietta, GA) allograft as an agent for joint and soft tissue pain reduction in the foot and ankle. Ultrasound-guided arthrocentesis using mDHACM allograft was performed on patients who were still experiencing localized joint and soft tissue pain after 12 months of ineffective conservative care. Both patients received an ultrasound-guided intra-articular, intra-tendon, and periarticular injection of mDHACM. The patients experienced reduced pain on ambulation 2 weeks after the treatment. Following the injections of mDHACM, patients were able to return to their daily activities with reduced pain.

Case 1

A 57-year-old male who was working as a machinist presented with a history of chronic left ankle inversion sprain, which first occurred in childhood, and bilateral pedal stress fractures that occurred while he was in the military. His chronic pain measured 6-10 out of 10 on the Wong–Baker FACES Pain Rating Scale.

The patient had undergone 8 months of conservative care consisting of ankle strapping, wearing high-top boots, and using custom orthotics. He had been taking nonsteroidal anti-inflammatory drugs (NSAIDs), had undergone phonophoresis, and was doing proprioceptive exercises, which had all failed to alleviate his symptoms. The patient was unable to have elective ankle and foot surgery because of job and family responsibilities.

Physical Examination

Upon physical examination, the patient’s dorsalis pedis and posterior tibial pulses were palpable and normal; temperature gradient of the lower extremity was within normal limits in both feet. Skin was supple and hydrated. Feet were not erythematous, warm, or swollen, and muscle power was normal—5 out of 5 for the dorsiflexors, plantar flexors, inverters, and evertors of both feet.

The patient has flexible pes planus (flat feet) with low-average arches. There was tenderness upon palpation along the peroneal tendons at the left ankle consistent with tendinitis. The patient described his pain as sharp shooting pain that radiated both proximally and distally or a dull ache. The pain on percussion was approximately 6 out of 10 on the Wong–Baker FACES Pain Rating Scale for the left ankle. The patient stated that rest alleviates the pain.

Radiographic Studies

An initial x-ray of the left ankle (AP, lateral, and oblique views) demonstrated no acute fracture or dislocation. The ankle mortise appeared maintained. There was a tiny plantar surface calcaneal spur. There were no lytic or blastic lesions and no soft tissue abnormalities.

Subsequently, an ankle MRI was obtained that showed a partial tear involving the left peroneus brevis, and tenosynovitis involving peroneus longus tendons with increased inflammation at the distal fibula, fibular groove, and extending 2 to 3 cm proximally. Also noted were left ligament sprains in the medial collateral ligaments, as well as at the lateral calcaneofibular and calcaneal talar ligaments. Boomerang-shaped peroneus brevis at the level of lateral malleolus was noted, indicating a dislocatable or dislocated peroneal tendon.

Clinical Course

The patient agreed to an ultrasound-guided injection of AmnioFix 40 mg particulate peritendon and intratendon to left peroneal tendon(s) at the distal fibula area (Figure 1). The patient’s ankle was then wrapped in a soft cast paste boot, and he was prescribed a postoperative shoe with instructions to remove the boot in 24 to 48 hours, and then return to usual footwear. The patient was also instructed to take NSAIDs in advance for expected post-injection pain. The Wong–Baker FACES Pain Rating Scale was used to rate average pre-injection pain from 0 (no hurt) to 10 (hurts worst), as well as the pain 8 weeks after the injections.

The patient returned to work after 2 days of weekend rest, with only use of an ankle support and wearing his high-top boots for ankle stability. He was able work a 40-hour week, and his pain level was reported at 1 to 2 out of 10 after 8 weeks. Although the pain was reduced, the patient continued to report tenderness (6-7/10) was present, “but not like it used to be.” Because of the structural abnormality of the boomerang peroneal tendon, it was expected that his pain may increase if the lateral ankle was not protected. Follow-up ultrasound of the same area 9 months later revealed decreased inflammation at the fibular groove and proximally. The patient will require surgical correction (Figure 2).

Case 2

This 40-year-old female veteran has a history of osteoarthritis and cervical dysplasia. She is actively employed as a college registrar. She presented with right foot pain at the right 3rd metatarsal phalangeal joint. Specifically the area is located in the region between the 3rd and 4th metatarsals of the right foot. The patient stated that the pain (7/10) was greatest when she wore high heels or put pressure on her forefoot. The patient stated that rest alleviated the pain, along with wearing a shoe that did not restrict her foot width. Previously, the patient was treated with 8 weeks of physical therapy that included phonophoresis with hydrocortisone ointment. The patient used her prescribed custom orthotics daily.  

Physical Examination

Physical examination of the patient’s dorsalis pedis and posterior tibial pulses showed healthy pulse (2 over 4 bilateral). Temperature gradient was within normal limits. Foot was not warm or swollen. Muscle power was 5 out of 5 for the dorsiflexors, plantar flexors, inverters, and evertors of both feet. There was tenderness upon palpation beneath the 3rd and 4th metatarsal heads of the right foot consistent with bursitis and neuroma pain. The patient described sharp, shooting pain radiating both proximally and distally. The pain was approximately 6 out of 10 for the right foot only.

Radiographic Studies

X-rays (AP, lateral, and oblique views) of the right foot demonstrated no acute fracture or dislocation. The joint spaces appeared preserved. There were no lytic or blastic lesions, and there were no soft tissue abnormalities. The MRI was negative for neuroma, but showed tenosynovitis of the flexor tendon of the 3rd digit at the level of the proximal phalanx.  

Clinical Course

The patient agreed to undergo ultrasound-guided injection of AmnioFix (40 mg) to the flexor tendon sheath at the 3rd interspace level, accessed through a dorsal approach (Figure 3). The patient was then wrapped in a soft cast paste boot and provided a postoperative shoe with instructions to remove the paste boot after 24 to 48 hours and then return to her usual shoes. The patient was instructed to premedicate with an NSAID to treat expected post-injection pain flare-up.

The Wong–Baker FACES Pain Rating Scale was used to rate her average pre- and post-injection pain. Eight weeks after the injection, the patient returned to work and was walking almost pain free (1/10) (Figure 4). Follow-up MRIs conducted at 6 and 10 months after injection revealed a small amount of fluid between the proximal 3rd and 4th metatarsals and the 4th extending into the 3rd interspace. A resolving plantar plate tear is suspected.

Discussion

Human amniotic membrane has been used in a variety of clinical applications for over 100 years.10-15 In vivo and in vitro studies have shown that the biochemical properties of amniotic membrane help to reduce inflammation and enhance soft tissue healing.14,16 In its natural form, human amniotic membrane has been shown to have antibacterial and pain reduction properties.5 Repair is mediated through the growth factors contained in the membrane tissue. These growth factors include epidural growth factor (EGF), transforming growth factor-beta (TGF-β), and fibroblast growth factor (FGF), which are known to stimulate epithelial cell migration and proliferation.

Platelet-derived growth factor (PDGF) A and B stimulate many metabolic processes, including general protein and collagen synthesis and collagenase activity, as well as chemotaxis of fibroblasts and smooth muscle cells. This can be effective for joint repair, as well as surrounding soft tissue repair, including tendons.5 TGF-β has been shown to significantly increase type I collagen production by tendon sheath fibroblasts.14,17

There is a method of cleaning, sterilizing, and drying human amniotic/chorionic membrane obtained from screened and tested donors to prevent the risk of disease transmission known as purion process.8 The aforementioned growth factors continue to be present in purion-processed dehydrated amniotic chorionic membrane.14,18 The mDHACM used in these cases is a purion-processed product from donated human tissue. According to the American Association of Tissue Banks (AATB) standards, mDHACM is considered a tissue product under section 361 of the Public Health Service Act. AmnioFix is minimally manipulated human amniotic/chorionic membrane intended for homologous use and is regulated as a human tissue by the US Food and Drug Administration. It is neither a medical device nor a drug, therefore it does not have to go through a 510(k) premarket approval or new drug application process because it contains no living cells.

The ability to inject dehydrated human amniotic membrane allows treatment of deeper soft tissue injuries rather than surface wounds alone. The purpose of these case presentations was to examine the feasibility and effectiveness of using mDHACM in suspension (0.9% saline solution) as an injectable treatment for refractory joint pain and healing of the immediate surrounding tissue.

As noted, the 2 patients received standard of care treatment (conservative treatment) for more than 1 year with little to no pain relief—rest, ice, compression, corticosteroid injection, stretching exercises, NSAIDs, and orthotics. Patients were excluded if they had prior surgery at the injection/joint site; clinical signs of site infection; evidence of significant neurological disease of the feet; or inability to ambulate. In addition patients were excluded if they had prior treatment with tissue engineered materials in the past 30 days or presence of the orthopedic comorbidities such as a foot or ankle stress fracture or nerve entrapment syndrome.

Diagnosis of localized joint arthralgia was confirmed by history and physical examination. The foot and ankle had to have circulation adequate for healing, determined by clinical signs and a Doppler ankle-arm index (AAI) >0.7.

The mDHACM was reconstituted with sterile 0.9% saline followed by intra-articular and periarticular injection of 0.9% saline plus mDHACM using a 25 gauge needle and 3 mL syringes. Using ultrasound-guided assistance, the needle was placed into joint, and the reconstituted mDHACM (1.5 mL) was injected. The needle was removed from the joint, and the remaining reconstituted product was placed periarticular, immediately surrounding the affected joint.

Conclusion

Traditionally, corticosteroid injection has been shown to provide relief from pain, although is associated with a high rate of relapse and may lead to permanent adverse changes within the joint and surrounding soft tissue structures.19 This review describes the clinical results of 2 patients with unresolved joint and local soft tissue pain who received a single-dose injection of mDHACM allograft and experienced significant improvement in symptoms, as well as increased function within 2 weeks of injection with sustained improvement over the 8-week follow-up.

The pain and related inflammation from both cases were structural in nature. Although corticosteroids may temporarily relieve pain, the amniotic product achieved the same results with growth factors that potentially help tissue healing. Further work is needed  to better assess the use of mDHACM within current treatment guidelines for the management of foot and ankle pain. Although there are many possible treatments for pain, no single treatment can be guaranteed based on quality of life measures that include comorbidities (obesity, diabetes), medication use, and lifestyle factors (smoking, malnutrition).20

Last updated on: March 5, 2019
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