Hyperbaric Oxygen and the Sickle Cell Leg Ulcer: One More Case, Still No Trial

Macro medical illustration of crescent-shaped sickled red blood cells crowding a narrowed capillary while oxygen molecules diffuse outward into pale tissue

A sickle cell leg ulcer is rarely a large wound. Two centimetres across is typical — a coin-sized crater sitting just below the inner ankle, with a necrotic centre. What makes it formidable is everything else about it: the pain that limits walking, the months of dressings, the tendency to recur, and the fact that the wound is the visible tip of a disease process involving chronic haemolysis, depleted nitric oxide, blocked capillaries, venous insufficiency and tissue that simply is not getting oxygen.

That last point is why hyperbaric oxygen therapy (HBOT) keeps appearing in this corner of medicine. If the problem is oxygen delivery, pressurized oxygen is the obvious lever. A case report published in September 2026 in Clinical Case Reports adds one more pleasant outcome to a file that is still, after decades, made up almost entirely of case reports.

The patient in Doha

The report comes from a haematology team at Hamad Medical Corporation in Qatar. Their patient was a 44-year-old man with homozygous sickle cell disease (HbSS) and long-standing chronic venous disease who arrived with a 2 × 2 cm ulcer on the medial side of the right ankle, about a month old, painful enough to make walking difficult, and unimproved after a course of oral antibiotics.

The workup was more thorough than the ulcer’s size suggests was necessary. Venous Doppler ultrasound found no acute deep vein thrombosis. Ankle radiography was normal. MRI excluded osteomyelitis and osteonecrosis. Laboratory results ruled out diabetes and clinically significant peripheral arterial disease. That matters, because in sickle cell disease an ulcer can be fed by several mechanisms in parallel, and the label “sickle cell leg ulcer” is only meaningful once the competing explanations are off the table.

After admission he improved enough to go home on oral clindamycin, fluids, analgesia, local wound care and compression — and then, one month later, the ulcer was still there. The team offered adjunctive HBOT. He completed nine sessions in a multiplace chamber over three weeks: three times weekly, 120 minutes per session at 1.5 atmospheres absolute (ATA), with two air breaks each time. He tolerated it without adverse events. Two months after finishing, the ulcer had contracted and nearly completely epithelialized, the pain had resolved, and he was walking normally again. No recurrence was seen during the available follow-up.

A pressure that deserves a second look

The protocol is worth pausing on. Wound-healing HBOT in clinical practice is usually delivered at 2.0 to 2.5 ATA — the range used in the cleared indications for diabetic lower-extremity wounds and compromised grafts and flaps. This patient was treated at 1.5 ATA, at the low end of what any centre would call clinical hyperbaric therapy and uncomfortably close to the mild pressures used in so-called “soft” chambers and the wellness market.

Whether 1.5 ATA is sufficient to drive angiogenesis and fibroblast activity in a hypoxic wound bed is not settled, and the case report offers no comparison against a higher dose. It is a detail a reader should hold onto: a good outcome at a mild dose in one patient is not evidence that a mild dose is sufficient — nor that the outcome was caused by the oxygen at all, since he continued standard wound care and compression throughout. The authors say as much themselves: “causality cannot be established from a single case.”

What the surrounding literature actually contains

The same Doha group published a narrative review of HBOT in sickle cell disease in Hemoglobin in May 2026. Its assessment of the field is blunt: evidence is “limited to case reports, small series, and early-phase studies with heterogeneous protocols,” with reported benefits in pain control and tissue healing in selected patients. HBOT “appears generally well tolerated, but its role remains undefined.”

The case literature is real but scattered. A 2023 report in Frontiers in Medicine described a 34-year-old man whose chronic ankle ulcer resolved completely after HBOT. A 2025 report in Undersea and Hyperbaric Medicine described a 35-year-old whose year-old ulcer closed after HBOT followed by skin grafting. A 2026 case report in the American Journal of Case Reports used adjuvant HBOT for bilateral humeral head avascular necrosis. Add a nine-patient pilot of HBOT for vaso-occlusive crisis in Diving and Hyperbaric Medicine in 2012, and the cumulative clinical experience is still measured in dozens of patients, not hundreds.

Mechanistically, the slogan version — pressurized oxygen “unsickles” the blood — has never been demonstrated in patients. A 2001 in-vitro study exposed blood samples from ten children with HbSS to 100% oxygen at 3 ATA and found no measurable change in sickle cell morphology. Whatever benefit HBOT may confer in sickle cell disease, the mechanism is more likely to be about oxygen delivery to starved tissue, inflammation and microvascular function than about reshaping red cells.

The trial that would answer the question is quiet

There is one randomized test in progress in this space, and it is not about ulcers. An international, triple-blinded trial called HBOT-SCD, whose protocol appeared in BMJ Open in November 2024, randomizes patients aged 8 and older having a vaso-occlusive crisis to HBOT at 2.0 ATA or sham at 1.3 ATA, with pain scores as the primary outcome, plus mechanistic and cost-effectiveness endpoints.

Its ClinicalTrials.gov record (NCT05289700), sponsored by Geneva University Hospitals, has not been updated since November 2022. The status field reads “unknown” — the registry’s term for a trial whose sponsor has stopped reporting. Recruitment targets and results are unstated. Anyone hoping that the coming years will deliver a definitive answer on HBOT for sickle cell complications should note how long this particular clock has been stopped.

The gold-standard review of the ulcer problem itself is starker still. The 2021 Cochrane review of interventions for sickle cell leg ulcers found six randomized trials, 198 participants and 250 ulcers — each trial testing a different drug, four of them sponsored by pharmaceutical companies, all at unclear or high risk of bias. Only one intervention (arginine butyrate) showed a reduction in ulcer size, on very low-certainty evidence. No trial reported time to complete healing, ulcer-free survival, quality of life, amputation or harms. And no trial of any non-pharmaceutical intervention — which means no HBOT trial — met the inclusion criteria at all.

Where the regulators stand

HBOT devices are Class II medical devices cleared by the FDA through the 510(k) pathway under Product Code CBF. The cleared indications — decompression sickness, carbon monoxide poisoning, certain non-healing diabetic wounds, late radiation tissue injury, gas gangrene, crush injury, severe anaemia, compromised skin grafts and flaps, idiopathic sudden sensorineural hearing loss, intracranial abscess — do not include sickle cell disease or sickle cell leg ulcers. Medicare’s National Coverage Determination 20.29 draws a similarly defined list, and sickle cell ulcers are not on it.

The FDA has also kept the hardware in view. Its letter to health care providers dated August 25, 2025 reminded facilities that the agency is aware of reports of serious injuries and deaths involving HBOT devices, including fires, and urged providers to follow manufacturer instructions, maintain fire prevention measures, train and monitor staff, and keep prohibited items out of chambers. That warning applies with particular force in cash-pay settings, where a patient with a chronic, painful, poorly evidenced condition is the most likely customer for an unproven indication.

What one case report is worth

A well-documented case is a hypothesis with a picture attached. It helps future researchers choose patients, dose and endpoints; it gives clinicians something concrete to weigh against the alternative of doing nothing; and it keeps a difficult problem visible. It is not proof of efficacy, and it cannot tell a patient with a leg ulcer whether HBOT will help them or how many sessions they should have.

The burden it sits against is not small. The CDC estimates sickle cell disease affects about 100,000 people in the United States, more than 90% of them non-Hispanic Black or African American, and that life expectancy is more than 20 years shorter than average — more than 30 years shorter when adjusted for quality of life. The agency also notes that many people with the disease do not receive recommended screenings and treatments, and that patients frequently report having their symptoms dismissed.

For now, the fair description of HBOT for a sickle cell leg ulcer is experimental adjunct: plausible, occasionally well photographed in the literature, unproven, unapproved for this purpose, and best pursued inside a study or registry with standard haematology care continuing alongside it. That framing is not a rejection of the Doha result. It is the framing its own authors asked for.

This article reports what published research and regulators say. It is not medical advice; treatment decisions belong with a patient’s own clinical team.

Sources

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