Treatment of Skin Severity in Ichthyosis with Hyperbaric Oxygen Therapy

Ichthyosis is a group of genetically and phenotypically heterogeneous skin
disorders characterized by dry, scaling skin. The skin may be thickened or very
thin and can have additional symptoms such as generalized redness and decreased
sweating. The underlying pathogenesis in this group is a decreased barrier
function of the skin. This barrier function is maintained by keratinocytes,
which are continually renewed from a stem cell pool in the basal layer of the
skin. When the cells migrate from the basal layer to the corneal layer, they
undergo physical and physiological changes, that are marked by, for example,
varying expression of proteins and the formation of a lipid barrier. This
migration is a complex process, with a high number of different components.
Mutation of these components may lead to a disruption of the process, with a
decreased barrier function, and therefore ichthyosis, as a phenotypical result.
Over 50 different mutations, the majority inherited, have been described that
all lead to ichthyosis. Common forms are ichthyosis vulgaris and X-linked
ichthyosis, with an estimated incidence of 1:250 and 1:6000 births,
respectively.

An immune profile study with ichthyosis skin samples showed increased epidermal
hyperplasia (increased thickness and keratin-16 expression) and T-cell and
dendritic cell infiltrates. Increased general inflammatory parameters as
(IL-2), innate (IL-1b), and some TH1/interferon (IFN-γ) markers in patients
with ichthyosis were comparable with those in patients with other inflammatory
diseases as psoriasis and atopic dermatitis. TNF-α levels in patients with
ichthyosis were also found to be increased. Chronic skin inflammation is
associated with increased inflammatory parameters such as IFN-γ, TNF-α, IL-4,
IL-5 IL-8, IL-13, I-CAM1.

In summary, patients with ichthyosis suffer from chronic inflammation and skin
infections because of the constant skin barrier impairment. These profound
comorbidities have a major impact on the quality of life. Severe desquamation,
pain and pruritus are common. A therapeutic attempt can be made with topical
calcineurin inhibitors or topical retinoids. Ciclosporin and intravenous
immunoglobulin replacement therapy (IVIG) have shown to be effective in
decreasing skin inflammation and itching in some patients. Still, patients
usually require daily topical treatment of the skin, including emollient and
mild immunosuppressive agents with an increased risk of systemic resorption and
side effects due to severe impaired skin barrier. Skin flares are often treated
with topical antibiotics, contributing to the already rising antibiotic
resistance in the dermatological practice. These side effects highlight the
need for alternative treatment options. Hyperbaric oxygen therapy (HBOT) may be
one option due to its anti-inflammatory and immune modulating effects.

Hyperbaric oxygen therapy
HBOT consists of breathing 100% oxygen under higher than normal atmospheric
pressure; usually 2.0-2.5 atmosphere absolute (ATA). This increases plasma and
tissue oxygen levels and decreases hypoxia. HBOT has been shown to alter
signaling pathways such as Hypoxia Induced Factor (HIF) and heme-oxygenase
(HO), both involved in tissue response to hypoxia and wound repair. The role of
these signaling pathways is increasingly appreciated for its anti-inflammatory
effects. Furthermore, the production of pro-inflammatory cytokines and
chemokines (IL-1, IL-6, TNF-α) is suppressed by HBOT. Also, in general,
oxidative stress is recognized to play a role in stem cell mobilization and
promoted skin healing because of the improved oxygenation and
neovascularization and decreases inflammation. A growing number of studies
support the benefits of HBOT therapy for enhancing wound healing and decreasing
the likelihood of negative events. A review of HBOT for the treatment of
radiation-induced skin necrosis also describes the beneficial effects on the
skin and healing process. The role of hypoxia and hypoxia-dependent signaling
pathways is also increasingly appreciated to add to the pathophysiology of
intestinal diseases, such as inflammatory bowel disease (IBD). HBOT has been
reported as a potential adjunctive treatment in patients suffering from IBD,
lowering inflammatory markers and oxidative stress.

There are few and usually mild side effects from HBOT. Patients have the risk
to suffer from barotraumas of the ears and sinuses. This risk is about 2-3%.
There is also a small risk to develop visual acuity changes, a reversible side
effect of the therapy. There is a very small risk (0.02-0.3%) of acute cerebral
oxygen toxicity. *

To assess clinical improvement of skin severity in patients with ichthyosis

Prospective cohort pilot study

Hyperbaric oxygen therapy

Overall, the risk of participating in this study is estimated to be low.
Patients could potentially benefit in terms of health and quality of life from
a long lasting or temporary decrease in their skin inflammation. Hyperbaric
oxygen therapy is routinely used in the treatment of different complex wound
healing problems. Side effects associated with HBO are mild.