Case 187: Case in Progress Followed 14 Years --- Neuropathic Ulcers, Osteomyelitis, Ischemia and Advanced Necrotizing Cellulitis in Patient Who Has Had Coronary Bypasses and Transplantations of Kidney and Pancreas.

Born July 26, 1954, this man had been a diabetic since 1978 (age 24). Standing 73 inches (185 cm) tall, he weighed 250 lb. at age 18 and 300 pounds at age 25. His foot problems began in 1985 (age 30) when in January he was admitted to a central Pennsylvania medical center with a right foot ulcer. After a prolonged hospitalization during which his ulcer area was grafted, he was placed on oral Clindamycin for six months. Within two weeks of stopping the Clindamycin, he developed a new ulcer which transiently healed. He did not respond to various outpatient treatments and was again admitted to the hospital on January 30th, 1986 with fever and poorly controlled diabetes of 24 hours duration. He had a swollen foot and redness about a plantar ulcer under his right first metatarsal head. His pedal pulses were 1+. He had a left foot drop, decreased vibration sense and bilateral retinal laser burns. He was given Mefoxin 1 gram intravenously every 4 hours. X-rays showed further progression and disarticulation of the first MTP joint. A repeat film February 12th revealed periosteal reaction along the diathesis of the first right metatarsal. On the 7th hospital day his infection penetrated through the dorsum of his right foot. An incision and drainage procedure was done and further cultures taken which did not reveal a possible oral antibiotic. Hence, he was given Claforan intravenously for a week that resulted in diarrhea and fever necessitating its discontinuance. He was advised that recurrence of his infection and an eventual leg amputation were likely. He was referred to Bryn Mawr for our therapies with local antibiotic injections and the Circulator Boot. His discharge diagnoses included osteomyelitis of the right foot, plantar ulcer of the right foot, cellulitis of the right foot, uncontrolled diabetes, retinopathy, neuropathy, left peroneal nerve palsy, and nontoxic goiter.

His local podiatrist treated him intermittently over the next few years when he developed new ulcerations under his right first metatarsal head. He continued to be fully ambulatory and work, perhaps explaining why he would improve but never heal his lesions. When the ulcer seemed especially troublesome, he came to Bryn Mawr for additional help. Thus, on December 30th, 1987, then 185 pounds, he presented with a blister under his right first metatarsal head. The ulcer had not responded to the Duricef and garamycin cream of his podiatrist. We treated him with the Mini-Boot and local gentamicin injections. Likewise, he returned November 6th, 1989 reporting that his ulcer had healed and remained healed until he vacationed in Mexico when he developed a new blister walking around in bare feet. He had returned to his local podiatrist who drained his blister and trimmed his callus weekly. He obtained a shoe with a metatarsal bar, but never permanently healed his lesion.

November 6th, 1989: Persistent plantar ulcer under his sesamoid bone.

November 6th, 1989: He participated in our research with cholinergic agents (see Dillon in our Neuropathy library). In this picture, PPG tracings of the plantar skin in the left foot are shown. Reactive hyperemia in response to local injection was increased by Methacholine compared to atropine.

On July 21st, 1990, he was admitted to Bryn Mawr Hospital. His ulcer had not healed and progressively more drainage had developed. On the 19th, he had become nauseated and lost control of his diabetes. On the morning of the 21st, his podiatrist found his foot swollen and advised the patient that oral or intravenous antibiotics would not likely help and that he would do well to return to Bryn Mawr for Boot therapy and local antibiotics. His history now included his having had some laser treatments to his retina, his use of a splint for his left foot to minimize his footdrop, and his possession and use of molded shoes with inserts that seemed to have no benefit for his feet. On physical examination he was found to have an oral temperature of 100 degrees F and a supine pulse 104 and blood pressure 142/88. His popliteal and femoral pulses were 2+ (easily palpable with firm palpation) and his dorsalis pedis and posterior tibials 1+ (definite but not easily found with firm palpation) bilaterally. Both light and firm touch sensations were absent in both feet.

July 21st, 1990: Under his 1st metatarsal head was an ulcer 1.6 cm in diameter with a fistula in its center in which the culture probe was introduced over an inch into the foot. The plantar skin under the big toe, first metatarsal and distal arch was slightly ruborous. A drop of serosanguineous drainage is seen dripping from the ulcer.

July 22nd, 1990: X-ray at Bryn Mawr Hospital: Marked soft tissue swelling around 1st metatarsal-phalangeal joint, some osteolysis of the head of the 1st metatarsal with some subluxation of the joint.... findings consistent with osteomyelitis within the head of the 1st metatarsal.

His admission laboratory data included a red cell sedimentation rate of 70 mm/hr, glycohemoglobin 20%, glucose 399 mg/dl, white count 10.9 and foot cultures eventually positive for abundant beta streptococci group B. Early in his hospitalization, his ulcer was irrigated with Sea Soaks containing gentamicin and vancomycin. Tobramycin and Ancef were initially administered intravenously. He was eager to get back on his feet and return to work. Hence, he was discharged on the following program: Bactrim-DS orally twice daily, a walking "Air Cast" with padding to spare his ulcer, sterile water cleansing soaks in the morning, three subsequent foot soaks using Sea Soaks containing 100 mg methacholine and 160 mg gentamicin per half gallon (Amphotericin B was also added to the soaks at the time of the treatment), Vasotec 10 mg daily, and NPH insulin 36 units before breakfast and 18 units at 10 PM. He also was given a scale of regular insulin to be taken before meals and at 10 PM that was based on his blood sugars. He was followed up in the Bryn Mawr boot clinic. .

October 10th, 1990. His foot appeared to be healed but because of recurrent callus and an elevated red cell sedimentation rate, local debridements and injections along with oral antibiotics were continued until the 20th of December.

On May 25th, 1991 he returned growing abundant Staphylococcus aureus from the plantar callus under the sesamoid of his big toe. He then received intermittent Mini-Boot treatments, local antibiotics injections and oral antibiotics along with debridements of his callus as necessary. Again, his ambulatory state prolonged his treatments which continued intermittently until February 1993.

August 25th, 1998: The dorsum of both feet were reddened, especially the left lateral foot. Ulcers on the right ankle, and 1st and 2nd toe are seen. In the left foot, a small spot of focal necrosis in the instep and maceration and infection of the middle three toes was found.

August 25th, 1998: The plantar aspect of the left foot had three large ulcers. Four toes in the right foot had large areas of necrosis. The right arch was pink. Areas of discoloration were present under his heel callus. He could sense none of these lesions. He was not able to sense the vibration of the electronic tuning fork (Bio-thesiometer) at maximum voltage.

August 26th, 1998: His distal pulses were absent in both feet while the left popliteal was faint to absent and a faint right popliteal was found with careful palpation. The femoral pulses were easily found with deep palpation. The pulse volume curves fell off progressively down both legs and were especially reduced at the left ankle and midfoot.

August 26th, 1998: The Doppler velocity of the right dorsalis pedis was 15 cm/sec but the curve was broadened and ragged. The right 1st dorsal metatarsal was low and the left essentially absent. The curves in the left foot were all monophasic and low. The left anterior tibial and dorsalis pedis were supplied by collaterals from the peroneal where local pressure obliterated distal flow in the two vessels. Medial calcinosis explained pseudohypertension at both ankles; his ankle/arm index was 1.52 at the right ankle and 1.23 at the left.

Hospitalization was recommended and refused. He preferred to try the previous outpatient treatment program he had had for several years. He was given samples of Trovan and begun on Mini-Boot treatments with local usage of gentamicin and vancomycin. While his temperature did drop, his left foot did not fare well. With his falloff in peripheral blood flow since 1993, he needed more booting... both Long- and Mini-Boot treatments.

September 1st, 1998: A medial view of the arch shows intense cellulitis up to the medial malleolus, severe necrotizing cellulitis of toes 1-4 and plantar callus with small foci of necrosis.

September 1st, 1998: In a more lateral view of the plantar aspect of the foot, the necrosis of the middle three toes is better appreciated. His previous three treatments and oral antibiotics obviously had not controlled the infection in his left foot where his arterial flow was most compromised.

September 1st, 1999. His right foot, however, was doing well. Here loose skin was pealing off as commonly happens after pumping in the Sea Soaks solution.

September 1st, 1998: X-rays of the left foot showed arterial calcifications, severe osteopenia and cortical loss of all of the distal phalanges, a fracture at the base of the 1st distal phalanx, gas in the soft tissues along the plantar aspect of the metatarsals (especially seen in the lateral view), swelling of the second toe with suspected osteomyelitis of the distal 2nd and 3rd toes.

The right foot showed dorsal dislocation of the 1st metatarsal-phalangeal joint with a lucent lesion in the 1st metatarsal head. The second proximal interphalangeal joint showed inflammatory changes suggesting osteomyelitis. Again, extensive arterial calcifications were seen.

He was found to be afebrile on admission September 1st. The cultures from an excision biopsy of the end of his 3rd toe were now reported as having produced a moderate growth of Coagulase-negative staphylococcus and heavy growths of Beta-hemolytic streptococcus, Enterococcus, Staphylococcus aureus and yeast. Physical findings of note besides his legs included bilateral gynecomastia, palpable masses in his left lower abdomen (his kidney transplant) and his right lower abdomen (his pancreatic transplant), and his thoracotomy scar. Laboratory findings through his hospitalization included an admission white count of 17.5 with 94% polys, 2 lymphocytes and 4 monocytes. His red cell sedimentation rate was 62 mm/hr and fell to 27 by October 16th. His admission albumen level was 2.5 grams/dl and did not rise into normal levels until October 23rd. His homocysteine level was 14.0 (slightly high) and his vitamin B12 was 285 (normal). His EKG showed sinus tachycardia with evidence of an old anterior wall infarct. He was begun on Unasyn 3 grams intravenously every 8 hours and vancomycin locally (both by injection and in the Sea Soaks solution within the Mini-Boot). Diflucan 100 mg was also given daily orally while Amphotericin B was also added to the Mini-Boot solutions. Urecholine was injected into the foot and added to the Sea Soaks to help stimulate vasodilatation in the foot. Rocaltrol was prescribed twice daily after September 26th. By September 17th, his lesions were clean enough to use Regranex on the cleaner areas to help speed epithelization. Bowing to forces promoting his discharge (the utilization nurse, his job and his obvious improvement), he was discharged October 24th, 1998. His discharge program included: Immuran 100 mg daily, Prograf 100 mg twice daily, Sea Soaks wet-to-dry soaks at home, Regranex applications nightly, Keflex 250 mg orally 4 times daily, stationary bike riding avoiding pressure on his heels or distal foot, and booting in the office with local administration of urecholine, vancomycin and gentamicin.

October 23rd, 1998. At the time of discharge from the hospital, his right foot was close to healed... and was declared healed on November 11th in the clinic.

October 23rd, 1998: The skin of the left foot was now normal in color but significant lesions remained in the distal foot to be healed.

His neuropathy persisted as a problem at home. He has not been able to use crutches without falling. He has tried using an Air-Cast on one leg without success. He tries to spare his distal left foot only to bear more weight on his heel. He lives alone in a three-story house making some ambulation necessary even if he does not try to go to work.... and without trying to go to work, he is at risk of losing his job. With his ambulation, hence, his left heel deteriorated. Timed with the breakdown of his heel was his usage of a new Air-Cast walking boot that came fitted with a hidden pad which slightly elevated his heel.

The plastic on his boot cracked and the company replaced his boot free of charge. However, this time a sponge was placed in the heel increasing pressure and stress on the heel of the patient.

The pad became apparent only when an overlying insole was removed.

He was again hospitalized in February. A 3+ growth of Stenotrophomonas (xanthomonas) maltophilia was recovered from his left foot. It was sensitive to trimethoprim/sulfa and levofloxacin and intermediate to ceftazidime and piperacillin. These sensitivities were to change over time. He remained in the hospital until June 26th, 1999. He was treated with intravenous Levoquin and local vancomycin, gentamicin and Urecholine. He received Mini-Boot treatments to both legs twice daily and Long-Boots to the left leg at least once daily.

January 21st, 1999: His central heel had broken down. Infection appeared to be lifting up the skin around the ulcer. Rubor of the distal foot again suggested new cellulitis.

February 4th, 1999: The loose superficial layer of skin has been debrided leaving a non-blanching hyperemic bare area with a black center of necrosis. The whole heel appeared in danger of necrosing. In the hospital, his foot was placed within a 100% oxygen environment in a plastic bag between his boot treatments and soaks.

February 16th, 1999: The left foot is shown with the film flipped to the PA view rather than the AP view. Only the proximal phalanx of the 4th toe is present and its end is somewhat demineralized. The body of the 3rd proximal phalanx is also somewhat demineralized. Vascular calcifications again are noted.

February 16th, 1999: No destructive lesions of the calcaneus were noted. The tissue pad under the calcaneus is well preserved.

April 28th, 1999: The end of the proximal phalanx of the 4th toe shows some demineralization. There is some periosteal cloaking around the mid-portion of the 3rd proximal phalanx. These areas were targeted for local antibiotics as his sedimentation rate was still elevated.

April 28th, 1999: The heel pad under the left foot is viewed from the opposite side versus above. A defect in the soft tissue is appreciated along with slight demineralization of the adjacent calcaneus. Again, this area is targeted with local antibiotics.

April 28th, 1999: The heel and the ulcer at the base of the 3rd toe remain to be healed. The skin elsewhere is healthy. The 1st, 2nd and 5th toes are essentially healed. The stub of the 4th toe is almost closed over. Work still to be done!.

May 18th, 1999: Diffuse soft tissue swelling was reported. A soft tissue defect was noted at the heel along with some demineralization of the calcaneus posteriorly and inferiorly consistent with osteomyelitis.

June, 1999: Pulse volume measurements show that the circulation to his left foot has benefited from his treatments. In the baseline study above, the "F" scale was used (each line equal to 0.2 mmHg pressure), the right foot and ankle had considerably better flow than the left foot and the waveforms were poorly developed in the left foot. Here, the "H" scale was used (each line equal to 0.3 mm Hg), the waveform at the left ankle is almost twice that at the right ankle, and the waveform in the left mid-foot is better formed and twice its original size. While the flow increased in the left foot, the flow in the right foot actually diminished since his baseline studies. The left foot was treated continually while treatment to the right foot ceased when it healed early in the course of his current episode.

As he was in the hospital until June 26th, he was off his feet and was able to receive almost daily treatment during June. He received 24 Long- and Mini-Boot treatments during the month. His program included intravenous Levaquin daily, local injections of Amikacin, ceftazidime and Urecholine and usage of Fungizone, Urecholine and ceftazidime in his Mini-Boot bath. He had become depressed and sick of being in the hospital.

July 15th, 1999: The toes are now healed. The ulcer under the 3rd-4th metatarsal heads is smaller. The convexity of his arch is better appreciated; he has been placing a sponge pad in the arch in an attempt to lessen the weight on his heel. The heel lesion is smaller, but the skin around the heel has become more red. There was little heel drainage to culture. When a culture was obtained on July 29th, the Stenotrophomonas maltophilia was found to still be present, but now was reported to be resistant to all antibiotics except ticarcillin (intermediate) and trimethoprin/sulfa. The latter was prescribed. Ticar proved difficult to obtain.

He was seen three days a week during July. He received injections of Amikacin, ceftazidime and Urecholine in his foot, a cleansing foot soak, and both a Long-Boot and a Mini-Boot (ceftazidime, Urecholine, and Fungizone in the bath) treatments. On July 29th, his heel was noted to be especially red with the redness extending somewhat up his Achilles tendon. His sed rate was increased to 38mm/hr. A tract into the heel pad was noted on the 31st; antibiotics were down the track with little resistance.

August 5th, 1999: The reddening of the heel continues to be prominent. The necrotic brown eschar has been occasionally cut back at its margins to allow the application of Reganex at the skin margins and new skin has continued to slowly fill in. Stenotrophomonas maltophilia was again cultured from the heel (same antibiotics profile). Bactrim-DS was continued and local Ticar was begun when it was obtained.

By the 3rd of August the fistula into his heel had become a deep tunnel. He was again advised to remain off his foot and to perform irrigations of his heel cavity with Sea Soaks containing Ticarcillin at home on the days he did not come to clinic. His heel color improved but bony fragments became palpable and he bled significantly after debridements. He continued with his 3 visits a week. Having no hospital days available on his insurance policy, he remained living in his mountain house.

August 17th, 1999: Increased destruction of the inferior posterior aspect of the os calcis with air or gas in the overlying soft tissues and increased soft tissue swelling again consistent with increased osteomyelitis.

August 17th, 1999: Absence of the distal 2nd, 3rd and 4th toes. Some resorption about the 3rd and 4th metatarsal heads.

He kept 11 foot clinic visits in October. He received a Long Boot treatment to the left leg and Mini-Boot treatments to both legs. Ticarcillin, ceftazidime and Urecholine were injected into his foot before the Mini-Boot treatments and both Fungizone and ceftazidime were added to the Mini-Boot bath for the left foot. His electrolytes, albumin, and hemoglobin were commonmly checked on a monthly basis. Frrom October 1998 to October 1999, his BUN varied from 14 to 20, his creatinine from 0.9 to 1.2, his albumin from 3.0 to 3.9 g/dl, and his hemoglobin from 9.8 to 15.5. The abnormal values were seen in October 1999 as he began to chronically bleed from his heel. Throughout the month, the importance of his remaining off his foot was emphasized. "One does not walk on fractures or bleeding ulcers." He remained, however, living alone in his mountain home. He could not use crutches and his walking cast was not providing protection for his heel.

October 12th, 1999: Further destruction of the os calcis with large ulceration on the plantar surface. Pathological fractures and small posterior seqestration.

October 12th, 1999: Previous resection of most of the distal phalanx of the 3rd toe and the middle and distal phalanges of the 4th toe. Past resection of the distal 2nd toe. Some bony loss and surface sclerosis of the heads of the 2nd and 3rd metatarsals... not the appearance of definite osteomyelitis.

On October 25th, his heel culture report showed a scant growth of Enterococcus species (sensitive to ampicillin, pennicillin and vancomycin) and a heavy growth of corynebacterium species. His program included heel irrigations with Sea Soaks containing ticarcillin and vancomycin was added to the Sea Soaks used in his Mini-Boot treatments. In Novembefr he had 11 clinic visits receiving both Long- and Mini-Boot treatments, foot soaks, and addition of ceftazidime and Fungizone to his Mini-Boot bath.

December 3rd, 1999: Hospitalization for beneath-the-knee amputation. The distal foot was essentially healed.

December 3rd, 1999: Loose bone fragments are seen in the heel ulcer.

His heel culture report returned December 4th showing now 2+ Pseudomonas aeruginosa (sensitive to ceftazidime, gentamicin, piperacillin and levofloxacin) and 1+ Staphylococcus coagulase-negative. The loss of bony structures below the left ankle shortened his leg and produced a "flail" foot. On the 12th of December, his left leg was amputated below the knee. The pathologist found areas of osteomyelitis, bone necrosis, bone resorption and new bone formation. Moderate to severe atherosclerosis with focal ossification was noted.

Comments: This gentleman has been presented as a case in progress. He illustrates many points. With his early obesity and uncontrolled diabetes, he rapidly developed advanced neuropathy. More gradually, he developed retinopathy and arteriosclerotic heart disease. With the help of contrast media, he developed renal failure. In contrast to this man, we have a small compulsive group with type I diabetics of 60 years duration without complications. He illustrates the penalties of poor control. Next, he illustrates the multiple difficulties related to neuropathy: muscle atrophy, lack of sensation, poor balance, recurrent ulcers and callus, minimal benefit from special shoewear, and poor response to the usual outpatient antibiotics. It is interesting to note that his hand function improved after his kidney transplant while his feet did not. His severe foot neuropathy persisted in spite of his not having diabetes for over three years. He still has atrophy of his thenar eminences, however. Our early Doppler studies showed high basal flow between pulse waves compatible with high flow due to arteriovenous shunting associated with his neuropathy (see Chew et al in our Neuropathy library); modest arterial calcifications were noted then. Subsequently, he received his pancreatic transplantation and was cured of his diabetes but not his neuropathy and high flow and peripheral calcifications persist. In some patients, our pumping appears to be associated with an improvement in sensation. Those benefiting, however, usually seem to be patients with less severe neuropathy. Finally, this man had the problem of his immunotherapy to prevent rejection of his transplants. If his immune system is sufficiently suppressed to avoid rejection, is it also suppressed sufficiently to promote his infections and to cause him to fail to recognize his damaged and gangrenous tissue. In spite of his extensive soft tissue infection, his osteomyelitis and significant tissue damage, we came close to healing his foot without major debridements. We used the Circulator Boot to restore arterial flow to the foot, Urecholine to help dilate the capillary beds and Regranex to help stimulate epithelization. Hospitalization was important! With two bad feet and poor balance, he had shown that he could not heal his lesions at home with ambulation; his left heel broke down at home after his 1998 hospitalization... and in July, 1999, his heel again became a problem when hospitalization was not an option. Precribed Air Casts and protective measures did not help him (see Litzelman et al in our epidemiology section). The long hospitalization he did have, while allowing his foot to heal, likely was associated with the development of osteoporosis in his foot thus predisposing his foot to Charcot fractures when he became ambulatory. As infection had been prominent in his episode beginning in August 1998, we had assumed it was still important in August 1999. A Charcot foot, however, may likewise be red and the disintegration of his foot was more akin to the Charcot destructive process than osteomyelitis; he did not have fever and pus that might have accompanied an extensive osteomyelitic process. Again, he showed that he was able to go from 1993 to 1998 without lesions if he was careful. He is relatively young. He has a good heart, a good mind, and a troublesome right knee prosthesis. We had hoped to heal both feet and get his right knee repaired. When his insurance did allow hospitalization, however, he had extensive destruction of his heel and lost his leg. Unfortunately, he is a good example of the speed and extent that Charcot damage can occur. The right leg survived a significant infection also. It now may have increased stresses due to the loss of the other leg. Hopefully, he is not too disheartened to take good care of it.