Case 149: Case in Progress: Osteomyelitis 5th Toe, Diabetic Neuritis Multiplex, Nephrosclerosis, Retinopathy and Congestive Heart Failure___ Diabetic Hypertensive Angiopathy.

Summary of Past Bryn Mawr Hospitalizations: (1) 11/10/71-11/14/71 35th week of pregnancy. Admitted for stabilization of diabetes mellitus present since age 10. (2) 11/24-11/30/71 Vaginal delivery of 8 pound 12 ounce APGAR #7 male baby. Baby did well except for "mild jaundice that was treated under the lamp." (3) 3/10-3/16/80: Left lower lobe pneumonia, 4 month pregnancy and diabetes mellitus. History of recent urinary tract infection treated with ampicillin. Highest admission blood pressure 158/90. (4) 6/14-6/24/80 Premature rupture of membranes leading to Cesarean section and delivery of 3 lb 2 oz male infant. (5) 9/22/93-9/28/93: Osteomyelitis left 5th toe, cellulitis of left foot and yeast esophagitis. Toe quickly responded to local injections of gentamicin, intravenous Timentin and Mini-Boot treatments. Esophagoscopy showed yeast infection. Discharged on oral nystatin and Fluconazole. Toe followed up in outpatient boot clinic and totally healed. (6) 1/20/95-1/22/95: Flu syndrome, diabetic ketosis and dehydration. Laboratory studies included a BUN of 10, a creatinine of 1.0 mg/dl, a normal urinalysis and a midstream urine culture growing 20,000 colonies of lactobaccili (normal vaginal inhabitants). Office follow-up blood pressure 146/77.

Interval notes: She hit her head and bleed badly on May 30th, 1996. She was taken to another hospital and sutured. The event was followed by amenorrhea leading to estrogen replacement. In March 1997, she traumatized her wrist and was given a prescription for Naprosyn; she retained some fluid and a rise in her blood pressure was noted. She was started on Accupril and prescribed a home sphygmomanometer to follow her blood pressure and adjust her medications. Noting good pressures at home, she discontinued her Accupril. In July, she took a vacation with her family which proved stressful. She returned complaining of blurry vision and general malaise; she was given the name of a retinal specialist. She was found to have a blood pressure of 182/85 with 3+ proteinuria and pyuria. She was given a course of Bactrim-DS successfully clearing her urine infection, but her proteinuria persisted. Her blood pressure remained elevated leading to the addition of Cardura to her blood pressure program. A modest elevation in her cholesterol led to a recheck of her TSH which was modestly elevated: Levothroid was also prescribed as was Lipitor several weeks later. On the 8th of September, she was examined by the retinal specialist. The latter noted a visual acuity of 20/30 O.D. and 20/200 O.S. He noted no proliferative changes in either eye. Numerous dot/blot hemorrhages were present in both eyes but were more numerous in the left eye. Fluorescein angiograms showed pinpoint areas of hyperfluorescence which on late angiograms showed leakage and macular edema. In the left eye, areas of capillary non-perfusion were seen within the macula explaining her decrease in vision. He offered no treatment for the capillary non-perfusion and recommended laser therapy as a means perhaps of slowing her disease. She did not return to the retina specialist for the therapy.

Florescein angiogram of left eye on September 8th, 1997.

Later views of left eye.

(7) 9/13/97-9/22/97: Discharge diagnoses: Urinary tract infection, laparoscopic cholecysectomy for cholecystitis, iron deficiency, normocytic anemia, arterial hypertension, hypothyroidism and diabetes mellitus. Fatigue, abdominal pain and shortness of breath led to her admission. She was close to her usual weight of 121 lbs. GI xrays showed minor signs of esophagitis. Her gallbladder ultrasound showed stones leading to the removal of an inflamed gallbladder. An MRI of the brain showed an old frontal stroke. Carotid flow studies showed shallow atherosclerotic disease. Her admission hemoglobin was 8.5 gm/dl and fell a few days later into the 7's; she received two units of packed cells prior to her surgery. Her reticulocyte count was 1.5%, serum iron 35 ug/dl, vitamin B12 274 (normal 211-911) and erythropoietin level 17.2 (normal under 27 at normal hemoglobin levels) prior to her transfusions. Her urine again grew a significant number of organisms: > 100,000 colonies of E-Coli. Her hypertension persisted leading to the increase of her Accupril to 80mg, the Cardura to 3 mg and introduction of Lopressor. Increased 2-point discrimination on admission (18cm), absent Achilles reflexes and failure to recognize the 5.10 fiber at 6 of 10 spots tested on her feet pointed to the presence of peripheral neuropathy. The possible benefits of boot therapy were discussed but, lacking a means of payment, no therapy was delivered. Interval note: She experienced a spontaneous bleed in her right bulbar conjunctiva on October 29th. Her blood pressure remained elevated leading to the addition of minoxidil 5mg to her routine medications. Her weight also began to increase suggesting fluid retention; furosemide was also added to her program. Increasing dypsnea led again to hospitalization. (8 ) 11/11/97-11/17/97: Discharge diagnoses included: Congestive heart failure and pyelonephritis. Her laboratory studies included an arterial PO2 of 58 mmHg on admission with a hemoglobin of 8.3gms/dl. Her white count was 11.5 and shifted to the left. Her serum albumen was 3.0 on day 1 and 2.6gm/dl on the second hospital day. Her serum iron was 19 ug/dl and 6% saturated. The erythropoietin was 19. The urine protein tested at 2+. The urine again grew out E-Coli. The renal ultrasound showed no hydronephrosis. The abdominal CAT scan showed bilateral pleural effusions and an irregularity of the right kidney cortex. Her echocardiogram showed billowing of the anterior mitral valve leaflet without discrete prolapse. Mild mitral regurgitation and mild dilatation of the left atrium were seen. The addition of digitalis to her therapy might have explained new RST changes on her EKG which otherwise might indicate arteriosclerotic heart disease. She was again transfused to benefit this time her respiratory effort and given Floxin for her urinary tract infection. Both minoxidil and Procardia SL were used as part of her antihypertension program. She was puffy on either or both but her blood pressure was better controlled.

Interval Note: After discharge her creatinine clearance was determined to be 29ml/min and her 24 hour urine protein 1003 mg/24 hr. She and her husband sought a conference and an explanation as to what had befallen her. Her records showed that she had been a regular visitor to our office during her early diabetic years and during her pregnancies. Thereafter, she had many absences of a few years between visits and had cut back considerably on her home testing. She had become a poorly-regulated diabetic and now had retinopathy, nephropathy, hypertension and peripheral neuropathy. Her recent urinary tract infections episodes and cholecystitis. The blow to her head and her small stroke may have played a role but were more likely sequellae rather than causes of her hypertension. Standard therapy included aggressive pharmacological therapy of her hypertension, tight control of her diabetes, long term antibiotic therapy and monitoring of her urinary tract infection, possible addition of erythropoietin for her anemia, diuretics for her fluid retention and avoidance of the nonsteroidal analgesics which had been associated with fluid retention. Actually all of the things she was doing...The possibility of renovascular hypertension and dilation of a renal artery was also discussed. Our renologists, however, were not enthusiastic about this possibility as previous patients like her had embolized and required dialysis. She was likely to require dialysis within the next few years and could become blind. In addition, she was now complaining of pain in the right leg down the L1 and L4 dermatomes. Her straight-leg raising test was normal; she appeared to have a mononeuritis multiplex. Having been treated in the Boot Clinic for her osteomyelitis, she was familiar with the boot and boot therapy made sense to her now that her leg also hurt. She was depressed, frequently crying at home and complained of just being sick. She weighed 134.3 pounds at the start of bilateral Long-Boot therapy.

She began to diurese immediately with her boot therapy; her sign says, "weight down 5 lbs. "Her facial puffiness is also beginning to resolve.

Her sense of well-being was improving as she posed during her boot treatment on the 2nd of January, 1998. Her sign reads:"1-2-98 9 treatments since last photo on 12-17-97"

Her diuresis continued to the first few weeks of January bring her weight to approximately 115 lbs. Her fatigue and anemia has persisted leading to the prescription of ferrous sulfate. Serial renal function tests are planned. Hopefully, she will return to her ophthalmologist for follow-up angiograms.

Comments: This lady illustrates several points. The Long-Boots are effective counterpulsation devices and increase cardiac output. They also increase the circulating levels of nitric oxide, prostacyclin and fibrinolysins and have effects on vascular beds outside of the leg. At an advanced stage in their diabetic complications, these patients develop a "hypertensive angiopathy" that may involve many vascular beds: head, eyes, kidneys, heart and nerves. Aggressive therapy of their hypertension is necessary to lower blood pressure but may be accompanied by anasarca as in this patient. We have had several patients come to us in these circumstances and respond nicely to the boot. Historically, we have not been quick to report these patients. Making too many claims clearly may undermine our credibility. We will add more details to her case as it progresses. Perhaps, the reader may have had another therapeutic option for this lady. We would be glad to hear about it.

Follow-up: She was seen by the ophthalmologist on April 6, 1998. He reported her visual acuity to be O.D. cc 20/30 and O.S. 20/70 ph NI. On this occasion he performed OIS digital angiography and noted fewer leaks than on her 9/8/97 study. He recommended that laser therapy be held back for the present and that she return for a repeat evaluation in three months. He repeated her angiograms .

OIS Digital angiography April 6, 1998.

As of April, her blood pressure was controlled and she felt better, but she continued to require her diuretics and anti-hypertension medications. Her weight on April 17th was 108.75 pounds, a weight perhaps representing dehydration and excessive use of the diuretics. Her creatinine clearance remained at 29 but her BUN had risen to 77mg/dl. She was asked to decrease her diuretics as tolerated. Feeling well and having transportation problems, she became irregular in her boot appointments perhaps getting treatments every other week during May and June. Our recommendation for boot treatments in her situation is Long-Boot treatments three times a week or more until her status is stable. Her BUN fell to 62 in early July, but she remains erratic in the control of her diabetes (Hgb A1c 11.2%). Erythropoieten has been prescribed for her anemia.