COVID-19 Wounds: Unusual Lower Extremity Bullae

Abstract

As the COVID-19 pandemic emerged, skin manifestations have been reported as part of this disease’s multisystem manifestations. While a rash similar to chilblains in acral distribution has been the most commonly reported complication, we noted a pattern of more severe lower extremity skin complications, specifically large bullae, in a series of COVID-19 patients.

Introduction

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19) met the definition of a pandemic. On that day, there were 3 COVID-19 patients hospitalized within our medical center—the Montefiore Health System in New York. By April 13, 2020, the COVID-19 surge had peaked in New York City, which had become the epicenter of the pandemic, with 1912 COVID-positive patients hospitalized on that day in our system.

Throughout this surge, and during the gradual downslope that ensued, the Montefiore Wound Healing Program continued its inpatient consultation service at 4 hospitals across Montefiore’s Bronx campuses.

With our hospitals converted to predominantly COVID-19 units, the wound team was consulted on a number of uncommon wounds that appeared uniquely related to COVID-19. COVID-related skin changes,^1,2 ranging from urticaria to the livedo reticularis and acral ischemia³ that came to be labeled as “COVID toes,” have been previously described.^4-6 This article adds to the literature on potentially COVID-related skin changes by describing a series of 3 cases of lower extremity bullae (2 hemorrhagic and 1 nonhemorrhagic) in patients hospitalized with COVID-19. Two of the bullae were extensive, in the range of 15 cm × 20 cm. Serious comorbidities were present in all 3 patients.

All 3 patients provided a signed consent for the publication of these photographs.

Case Reports

Case 1

A 52-year-old man was admitted with fever, fatigue, and shortness of breath that began 3 days prior to admission. His past medical history is significant for morbid obesity, nonischemic cardiomyopathy status post orthotopic heart transplantation in 2015, hypertension, diabetes mellitus, and pulmonary sarcoidosis. The patient was found to be COVID-19 positive. At the time of admission, laboratory values included white blood cell (WBC) count 3700/µL, hemoglobin 13.9 g/dL, hematocrit 46.0%, platelets 133 000/µL, albumin 4.5 g/dL, D-dimer 0.38 µg/mL, fibrinogen 638 mg/dL (on third hospitalization day; it was not measured on admission day), and C-reactive protein (CRP) 4.5 mg/dL on admission and 13.1 mg/L on the third day. The patient required intubation and daily prone positioning while in the intensive care unit as well as initiation of vasopressor agents (norepinephrine and vasopressin) for vasodilatory shock. Renal function worsened requiring CVVH (continuing veno-venous hemofiltration). The patient was treated with a 10-day course of hydroxychloroquine, and 1-day of remdesivir before it was stopped because of worsening renal status. The patient was also started on anticoagulation therapy (bivalirudin) as per protocol, and despite the treatment, on hospital day 18, he had developed a left lower extremity deep vein thrombosis (DVT). This patient was not on steroids; mycophenolic acid was held in the setting of acute infection and tacrolimus dose was adjusted for renal function to maintain a level of 5 to 7. Additionally, antibiotics were started for coinfection with bacterial pneumonia and urinary tract infection. He received vancomycin, piperacillin-tazobactam, meropenem, and cefepime at different points early in hospitalization.

Approximately 20 days after admission and 5 days following extubation, a left lower extremity bulla was noted extending from medial malleolus across the whole plantar surface of the foot, measuring 10 cm × 20 cm (Figure 1a). At time of bulla formation, a venous duplex study revealed an acute DVT of the left common femoral, femoral, and popliteal veins. Laboratory values at that time included WBC count 8100/µL, hemoglobin 6.9 g/dL, hematocrit 23.5%, platelets 189 000/µL, international normalized ratio (INR) 2.2, prothrombin time 25.2 seconds, partial thromboplastin time (PTT) 63.3 seconds, D-dimer >20 µg/mL, albumin 3.1 g/dL, CRP 4.5 mg/L (from 12.6 mg/L 3 days prior), fibrinogen 292 mg/dL (from 622 mg/dL 3 days prior), haptoglobin 216 mg/dL, ferritin 903 ng/mL, antithrombin III 92% (within normal range), and serum interleukin-6 23.68 pg/mL (high).

Figure 1.

(a) Large hemorrhagic bulla on the left foot measuring 10 cm × 20 cm. (b) Same patient exhibiting “COVID-toe.”

Of note, in addition to this bulla, the patient’s left hallux displayed distal ischemia consistent with “COVID-toe” (b). This was first noted over 3 weeks after vasopressors were stopped, and so was unlikely to be related to the vasopressors.

This extensive bulla caused the patient significant amount of pain. Also, on inspection and cautious palpation, we felt that a thrombus appeared to be forming within. An attempt was made to aspirate the fluid with an 18-G needle but was unsuccessful. The blister was incised with a scalpel and drained. There were indeed formed clots that were removed. Specimen was not sent for pathology. Being on the plantar surface, the patient’s skin was slightly calloused and thick. We decided to let it heal by secondary intention and recommended daily cleansing and wrapping in rolled gauze.

The decision for incision and drainage (I&D) in this patient was based on the pain he experienced, his immunocompromised status, and concern for hematoma formation with a risk of infection. At the time of I&D, the patient was completely stable and ready to be discharged home. He tolerated the procedure well and was discharged 2 days later. Total hospital stay was 50 days. The patient was discharged with home care 3 times a week and wound-care recommendations as above. On follow-up televisit 3 weeks after discharge, the patient reported that the wound was nearly healed.

Case 2

A 67-year-old man was admitted with worsening cough and was diagnosed with COVID-19 pneumonia. Past medical history included gastric adenocarcinoma on chemotherapy, human immunodeficiency virus on antiretroviral therapy with abacavir/dolutegravir/lamivudine, diabetes mellitus, hypertension, and stage IV chronic kidney disease. His HIV viral load was undetectable and CD4 count was 453 cells/µL. He last had received chemotherapy 9 days prior to admission, including fluorouracil, leucovorin, oxaliplatin, docetaxel, and dexamethasone; and he received pegfilgrastim 8 days prior to admission. At the time of admission, laboratory values included WBC 7500/µL, hemoglobin 9.7 g/dL, hematocrit 29.4%, platelets 113 000/µL, D-dimer 2.67 µg/mL, fibrinogen 835 mg/dL, and CRP 1.3 mg/L. The patient’s hospital course was complicated by sepsis, encephalopathy, acute renal failure requiring hemodialysis, and anemia requiring transfusion. Renal function subsequently improved and a tunneled catheter was removed. The patient was not placed on anticoagulants due to a history of gastrointestinal bleed. The patient was treated with hydroxychloroquine but was not on remdesivir or steroids.

A left plantar bulla noted on hospital day 11 (Figure 2). It measured 10 cm × 10 cm, filled with serous fluid, noticed to be oozing by small amounts. At the time of bulla formation, the laboratory values were as follows: WBC 7300/µL, hemoglobin 7.8 g/dL, hematocrit 24.4%, platelets 271 000/µL, INR 1.0, PTT 38.3 seconds, D-dimer 1.98 µg/mL, and albumin 2.7 g/dL. A venous duplex study had been done 9 days prior to bulla formation and was negative.

Figure 2.

Left plantar bulla was 10 cm × 10 cm filled with clear fluid, not tense or painful.

Here, we left the bulla intact, as it was smaller, nontender, and did not have a significant amount of fluid. The wound was cleansed and wrapped; an offloading shoe was obtained at the time of discharge. The patient was discharged home from the hospital after 13 days but was readmitted soon after for abdominal pain related to gastric carcinoma with mass of the right hepatic lobe, worsening renal function, and need for placement of a hemodialysis access catheter. There was no mention of the plantar blister in the medical record on readmission. We followed-up with the patient via telemedicine; he reported that the wound is completely healed and does not bother him.

Case 3

A 53-year-old woman presented with fever and cough that began 2 days prior to admission and was diagnosed with COVID-19 pneumonia. Past medical history included morbid obesity, history of pulmonary embolus (in 2015 after knee surgery, followed by anticoagulation therapy for 6 months), hypertension, anemia, and obstructive sleep apnea. On admission, laboratory values included WBC count 15600/µL, hemoglobin 14 g/dL, hematocrit 41.3%, platelets 181 000/µL, INR 6.3, prothrombin time 16.3 seconds, PTT 37.6 seconds, albumin 3.6 g/dL, ferritin 650 ng/mL, CRP 37.9, fibrinogen 786 mg/dL, D-dimer >20 µg/mL, and CRP 13.4 mg/L. The patient was treated with hydroxychloroquine, intravenous steroids, and intravenous antibiotics for pneumonia and urinary tract infection. Antibiotics included vancomycin, piperacillin-tazobactam, and cefepime. As per protocol, therapeutic dose enoxaparin therapy was initiated, but the patient developed a retroperitoneal bleed with bilateral psoas hematomas and it was discontinued. Venous duplex study was negative for DVT on hospitalization day 13.

Two hemorrhagic bullae, one on the right leg and another on the left ankle, were present at the time of admission. The patient informed us that she started experiencing symptoms a few days prior to admission but was scared to come to the hospital. A wound care consultation was requested after the bulla on the right had ruptured spontaneously revealed a clean base and partial epidermal loss (Figure 3a).

Figure 3.

(a) Bulla on the right leg after a spontaneous rupture and partial epidermal loss. (b) Larger bulla on the left ankle. (c) Bulla on the left ankle after a spontaneous rupture with a large thrombus in the wound cavity. (d) Wound after a partial surgical evacuation of hematoma.

However, the larger bulla on the left ankle (Figure 3b) was still intact at the time of the initial consult. A decision was made to cover with protective dressings and offload. Nine days later, this bulla ruptured and turned into an open wound with a hematoma and a massive clot in place (Figure 3c).

The initial treatment plan of this open wound was to allow for clot resorption with daily cleansing, bismuth-petrolatum mesh dressing (Xeroform) application, and gauze wrapping of the foot and ankle. However, the wound continued to appear worse and eventually some of the hematoma was evacuated by vascular surgery (Figure 3d).

The patient was discharged to a skilled nursing facility for subacute rehabilitation after a hospital stay of 24 days.

This patient was readmitted about a week later with multiple bilateral pulmonary embolisms, requiring a left pulmonary arterial thrombectomy and inferior vena cava filter placement. One month after bulla formation during a readmission, a venous duplex revealed DVT in the common femoral and proximal-mid femoral veins and on the left leg DVT noted of the common femoral, femoral, and popliteal veins.

At most recent follow-up, the wounds were both contracting with areas of new epithelialization at the edges.

Conclusion

All 3 patients we described had risk factors for hypercoagulable state—previous history of pulmonary embolism, malignancy, and obesity. In addition, coagulation function in patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is significantly deranged⁷ supporting hypercoagulability with severe inflammatory state.⁸ At the time when these 3 patients were admitted, treatment algorithms were still rapidly evolving. Patients who test positive for COVID-19 at our institution now are fully anticoagulated if D-dimer >3 µg/mL and prophylactically anticoagulated if D-dimer <3 µg/mL, unless contraindicated. In addition, morbid obesity (in 2 of 3 patients described), fluid retention, and prolonged hospitalization all precipitated epidermal lysis with possible pressure/shearing factors contributing, while on bedrest.

The treatment approach to these extensive bullae was challenging, as the prevailing thought is to leave blisters intact. Colleagues from dermatology and vascular surgery were consulted by the primary team as well and all recommended not to disturb these blisters and wrap them in gauze. There is no consensus on how to treat these extensive bullae. In addition to the cases described, there were at least 2 other patients with plantar/ankle bullae, but they were not as extensive. The main reason why we did not submit the specimen to pathology after I&D on the first patient we described is that at the time we did not think this bulla was COVID-related. We attributed the etiology to pressure injury. It is only after noticing similar findings in COVID-infected patients we drew a parallel between the cases.

We recommend that these blisters be evaluated and treated individually, in some cases by leaving it intact, especially if it is a bulla filled with serous fluid, smaller in size, and not on plantar surface. Bullae on the plantar surface of the foot also need to be assessed individually: in the cases we presented, one patient benefited from I&D and another —from leaving it to resorb on its own. Large hemorrhagic bullae may benefit from evacuation before thrombi have formed to facilitate a safe procedure. On the last patient we described, the ruptured bullae had a large clot formed that started to bleed when the thrombus was slightly disturbed; this required consultation with vascular surgery to complete the removal. The procedure also can be painful since thrombi adhere to the dermis and often not easy to remove.

This is an early report and needs further exploration with follow-up to healing for surviving patients and evaluation of pathological specimens, as well as contextualization within evolving understanding of the pathophysiology of COVID-19 and of optimal treatment protocols. We think similar cases will be apparent soon in hospitals across the country where wound care providers will be called for recommendation. It would also be helpful to determine factors that lead to their formation and that expedite their healing.