Occasional Review

Use of Hyperbaric Oxygen in Rheumatic Diseases: And Critical Analysis
D.J. Wallace 1,2 S. Silverman.2* J.Goldstein 3,and D. Hughes 4
1Department of Medicine Cedar-Sinai Medical Center 2UCLA School of Medicine, Los Angeles, CA. 3 The Chronic Fatigue Syndrome Institute. Anaheim CA. And 4 The Hyperbaric Oxygen Institute, San Bernardino, CA USA

Hyperbaric Oxygen has been used in patients with rheumatic disease for many years with out reports of untoward or unusual complications for a variety of non-rheumatic indications. Recent evidence that hyperbaric oxygen inhibits the actions of certain cytokines, acts as an immune doculator, and might help cognitive dysfunction has resulted in a re-examination of its potential role in rheumatic diseases. A case report of a LUPUS/ Scleroderma crossover patient is presented whose cognitive dysfunction improved after hyperbaric oxygen therapy. The history of hyperbaric oxygen and its physiology are related, along with a focused review of its effects on the immune and central nervous systems. Areas which might warrant further consideration by rheumatologists are outlined, as well as areas of concern.

Hyperbaric oxygen, Scleroderma, rheumatic Diseases

Hyperbaric Oxygen Therapy is defined as the subjecting of patients to pure oxygen breathing at ambient temperatures, which are greater than normal atmospheric pressure.

Although concepts of hyperbaric oxygen therapy were first employed in 1662, its modern use other than for decompression dates from 1956, when hyperbaric oxygen was used to perform cardiac surgery in Holland 1. Mechanically, the most common applications of hyperbaric oxygen are to dissolve air or gas emboli and treat divers with “bends” or decompression illness.

New insights into the biochemical and immune interactions of hyperbaric oxygen have increased interest in its potential applications over the past decade. The United States Medicare System has approved hyperbaric oxygen for 13 indications ranging from acute carbon monoxide intoxication, gas gangrene, and osteoradionecrosis to acute arterial insufficiency. Over the last 20 years, patients with a variety of conditions, especially multiple sclerosis, have reported cognitive improvement after undergoing hyperbaric oxygen. One lupus/ scleroderma crossover patient, whose case is reported here, underwent hyperbaric oxygen therapy specifically for cognitive impairment and experienced subjective and objective improvements. Her case is presented and our concepts of hyperbaric oxygen and the immune and central systems are reviewed.

Case Report:
A 53-year-old Caucasian woman was a flight attendant in an usual state of health in 1979 when she underwent a thyroidectomy and inadvertent parathyroidectomy for Graves disease. In February 1980, her Heyer-Schulte saline breast implants (placed in 1977 for cosmetic purposes) were replaced with Cox-Uphoff Silicone prostheses. She was well until 1986, when she presented to UCLA Medical Center with subcutaneous arthritis, Raynaud’s phenomenon, Sclerodactyly, inflammatory arthritis, and erythematous rashes. A work-up demonstrated an ANA of 1:40 (speckled), elevated sedimentation rates (averaging in the high 30s) and persistently decreased IgA levels. She was diagnosed as having a lupus/ scleroderma crossover, although the possibility of eosinophilic fascuiitis was considered. (It was ultimately ascertained that she occasionally took Ltroptophan to sleep after long fights.) No disease modifying therapy was given. Supportive diuresis and not steroidal anti-inflammatory agents were prescribed.

Over the following seven years, her ANA rose to 1:1280 (homogeneous) a positive IgG anticardiolipin antibody was found, and her course was complicated by percarditis and supraventrocular tachyarrhythmias. The latter two items were felt to be suggestive of cardiac sclerodrema. Anti RNP was negative and her inflammatory arthritis subsided. CD3 levels. B cell and natural killer cell values do not change. Similar findings have been found in mice in two separate studies. 9.10 Interestingly, the administration of Immunoglobulin production by spleen cells 9 Long-terms hyperbaric oxygen delayed the development of Proteinuria, facial erythema, and lymphadenopathy in an MRI./ 1pr. Mice. Iamoto et al showed that hyperbaric oxygen has immunosuppressive properties modulated by decreasing interluekin 1 and prostaglandin E2 production, but interleukin 6 in production was not altered. 11

How does Hyperbaric Oxygen Affect the Central Nervous System?

Studies of hyperbaric oxygen on the central nervous system show that at tensions of 1.2- 1.5 atmospheres absolute (ATA), it decreases blood flow by 1% to 20%. (Mean of various studies is about 10%.) Two other physiological changes occur. These include greater permeability of the blood brain barrier to medications and increased oxygen tensions tissues that far outweigh the net effects of mild vasoconstriction. The deformability of erythrocytes is increased resulting in improved transportation in the microvasculature circulation and lactate removal. 12

Hyperbaric oxygen stimulates the metabolism of nerve cells deprived of oxygen. As early as the 1960s, Meijne reported cognitive improvement in patients to performing mathematical calculations and demonstrated increased typewriter skills after hyperbaric oxygen. 13 An area of controversy among Hyperbaricists concerns the possibility that once 1.5 ATA is exceeded, anaerobic metabolism is favored, and thus cognitive results do not improve as well as they would at lower pressures. Di Sabato et al 14 performed a controlled study (with Sham hyperbaric controls) on patients with cluster headaches. The dramatic improvement was attributed to vasoconstriction, decreased edema, increased serotoin synthesis, and decreased cerebral hypoxia. Additionally, in the central nervous system hyperbaric oxygen decreases adrenaline and monoamine oxidase levels as well as promoting axonal regeneration 15.


Hyperbaric Oxygen for Multiple Sclerosis and other autoimmune diseases

As hyperbaric oxygen decreases demyelination from per-vascular edema, more than 6000 patients with multiple sclerosis have undergone this therapy in the past ten years. A published trial by The New England Journal of Medicine suggesting improvement with hyperbaric oxygen in 40 patients in 1983 stimulated considerable interest. 16 However, it was evident that even though hyperbaric oxygen increased helper T lymphocyte levels, patient liked the treatment and reported subjective improvements (especially in the sense of well-being, cognitions and bladder function), four separated placebo-controlled double-blind trials failed to demonstrate any objective benefits of using the Kutz Disability status Scale or any other parameters 17-20 This was also confirmed in a 22 institution multicenter registry 312 patients followed for 2 years. 21 Occasionally patients with other rheumatic syndromes and associated complications have been held to respond to hyperbaric oxygen. Aseptic necrosis complicating system lupus, for example, appears to be worthy of greater scrutiny. Abstracts and presentations at seminars and meetings of hyperbaric oxygen claim benefits for pneumatosis cystoid intestinal in sclerodrema, livedo reticularis with Vasculitis and Raynaud’s phenomenon. Articles have appeared advocating hyperbaric oxygen for Crohn’s disease and cyclophophadmide-associated hemorrhagic cystitis

How safe is hyperbaric oxygen?

Hyperbaric Oxygen is generally quite safe, but serious complications can occur.24 Absolute contraindications to hyperbaric oxygen include pregnancy, underlying malignancy, untreated PNEUMOTHORAX, concomitant therapy with doxorubicin, cis-platinum, or disulfiram. Special considerations need to be taken into account if the patient has upper respiratory tract infections or chronic sinusitis (which make clearing of the ears and sinuses problematic), low seizure thresholds (with high fevers or epilepsy, emphysema with CO2 retention (which suppresses breathing), and congenital spherocytosis (where hemolysis can result).

The most common complication of hyperbaric oxygen is barotrauma to the ears and sinuses caused by pressure changes, which has been reported in about 5% of the cases. Occurring in 0.1- 5% of the patients are hypersensitivity reactions confinement anxiety, central nervous system oxygen toxicity, pulmonary oxygen toxicity and temporary changes in eyesight. To minimize risks, patients are advised to have an ear, nose and throat examination by the treating physician before therapy, not to drink alcohol or take any medication for four hours prior to treatment, and to wear 100% cotton clothing.


Is there a potential role for hyperbaric oxygen in Rheumatic Diseases?

Very little is known about the influence of hyperbaric oxygen on the immune system. Animal models of autoimmune disease and normal mice are conductive to hyperbaric oxygen studies. Hyperbaric oxygen might be useful in combination with other therapeutic modalities. Further study is needed in these areas before proceeding to human trials. Nevertheless, anecdotal testimonials that hyperbaric oxygen helps people think more clearly should be taken seriously and ultimately subjected to a prospective trial. Systemic lupus erthematosus (SLE) is an autoimmune disorder that affects several hundred thousand Americans. Nearly half manifest in similar cognitive deficits that do not respond to CORTICOSTEROIDS. 26 In the past few years, the development of single photon emission computerized tomography (SPECT) has shown hypoperfusion abnormalities bitemporally and bifrontally in patients with SLE and incidentally, with fibromyalgia/chronic fatigue syndromes. 26-29

Hyperbaric oxygen is a well-characterized, old technology whose immunodulatory properties and effects on cognition have never been adequately studied. Although relatively expensive, this reasonably safe procedure might have potential heretofore-unrealized applications to the patients with rheumatic disease.
Bojic L., Gosovic S., Kovacecic H., and Denoble P. Hyperbaric Oxygenation in the Treatment of Macular
Degeneration. Split, Yugoslavia: Split Naval Medical Institute, pp. 1-4.

Dr. L. Bojic treated four patients with advanced macular degeneration and severe vision loss in a clinical trail with HBOT. Three of the four patients experienced a doubling of visual acuity after HBOT. The fourth patient experienced a four-fold improvement.
Although much more research is needed and HBOT must be considered experimental in this condition, it seems that a trial of 30 90-minute treatments at 1.5 ATA in a monoplace HBO chamber, combined with other therapies such as laser and nutritional supplements, offers hope for additional benefit. This makes good sense, because cells of the retina are specialized neurons — actually an extension of the brain. Retinal cells would therefore be expected to respond to HBOT, similarly to brain-injured patients.