Molecular hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers
Erythema is a redness of the skin that pales when pressed. Erythema is the result of dilation of the skin blood vessels.
– Generalized erythema has the cause of either an allergy to a drug or an infectious disease (scarlet fever, measles, rubella, epidemic megalithitis, syphilis exantem suddenly).
– Localized erythema may have a physical (insolation), chemical (artificial dermis), drug (fixed pigmented erythema), infectious (intertrigo, erysipel, erizipeloid, pasteurellosis, trichinosis) or dermatological (dermatomyositis, lupus erythematosus) cause.
We have treated 4 patients of acute erythematous skin diseases with fever and/or pain by molecular hydrogen H2 enriched intravenous fluid. We also added data from two volunteers for assessing the mode of molecular hydrogen H2 delivery to the skin for evaluation of feasibility of molecular hydrogen H2 treatment for this type of skin diseases.
All of the four patients received intravenous administration of 500 ml of molecular hydrogen H2 enriched fluid in 30 min for more than 3 days except in one patient for only once. From two volunteers (one for intravenous molecular hydrogen H2 administration and the other for molecular hydrogen H2 inhalation), blood samples were withdrawn serially and air samples were collected from a heavy duty plastic bag covering a leg, before, during and after molecular hydrogen H2 administration. These samples were checked for molecular hydrogen H2 concentration immediately by gas chromatography. Multiple physiological parameters and blood chemistry data were collected also.
Erythema of these 4 patients and associated symptoms improved significantly after the molecular hydrogen H2 treatment and did not recur.
Administration of molecular hydrogen H2 did not change physiological parameters and did not cause deterioration of the blood chemistry. The molecular hydrogen H2 concentration in the blood from the volunteers rapidly increased with molecular hydrogen H2 inhalation and slowly decreased with cessation of molecular hydrogen H2 particularly in the venous blood, while molecular hydrogen H2 concentration of the air from the surface of the leg showed much slower changes even after molecular hydrogen H2 inhalation was discontinued, at least during the time of sample collection.
An improvement in acute erythemtous skin diseases followed the administration of molecular hydrogen H2 enriched fluid without compromising the safety. The molecular hydrogen H2 delivery study of two volunteers suggested initial direct delivery and additional prolonged delivery possibly from a slowly desaturating reservoir in the skin to the surface.
Severe and acute erythematous skin diseases usually require immediate medical attention, particularly when the symptoms involve severe pain and/or fever. Treatment may have to be initiated before spending enough time and effort for investigating real causes of the rush or functional state of the other organs and the steroid agents tend to be the first choice of the treatment. However, the complications from the general use of steroid have been well known and therefore, non-dermatological clinics like ours frequently encounter difficulty in finding quick remedies with minimal side effects. Erythema is reddening of the skin due to inflammatory mechanisms either as primary culprits or secondary features and locally released inflammatory cytokines such as TNF-α, IL-1,8, GM-CSF etc., stimulate phagocytes and inflammatory cells and results in production of ROS (reactive oxygen species)[1, 2]. The interaction between the ROS and nitric oxide leads to the formation of peroxynitrite radicals and also by the iron-mediated Fenton reaction, hydroxyl radicals, both of which are highly reactive and destructive to the cell membrane and mitochondria and polyunsaturated fatty acids(PUFAs) . However, ROS dismutases, which are abundant in the skin and also currently available medications are ineffective to neutralize these most destructive radicals except Edaravone , of which use is strictly limited for the treatment of acute cerebral infarction patients with normal kidney and liver function.
molecular hydrogen H2 may be useful in these situations because it immediately and simultaneously neutralizes both peroxynitrites and hydroxyl radicals  and also molecular hydrogen H2 is known to cause no significant side effects since it is produced in the human intestine as a fermentation process, although not continuously.
We report four cases of acute erythematous skin disease patients who were suffering from skin rash and also from associated symptoms such as severe pain and/or fever. They were treated with regular medications first and when the conventional treatments failed, then, intravenous fluids which contained molecular hydrogen H2 were added after a proper consent form was signed. However, molecular hydrogen H2 administration may not be therapeutic unless enough concentration stays at the surface layer of the skin for a sufficient period and the concentration should be higher than that of internally produced molecular hydrogen H2. Two volunteers participated in a molecular hydrogen H2 delivery study where molecular hydrogen H2 concentration in the blood and in the air at the surface of the skin was measured before, during and after molecular hydrogen H2 administration by inhalation or by intravenous fluid infusion.
Patients and volunteers
Before recruiting the patients and volunteers to the current study, a complete PARQ conference was given to all of the patients and their family and to volunteers. Our specific consent form, which had been approved by the Nishijima Hospital Ethics Committee and the Nishijima Hospital Pharmacists Council, was signed before the study with clear understanding of the nature of the study.
Case history of 4 patients
48 y.o. male who was in good health until 5 days prior to the admission to Nishijima Hospital when severe pain and skin rash involving his left side of the face made him to visit an emergency service where he was diagnosed as having herpes simplex infection and was treated with antivirus agents and pain medications. However, the pain increased and the left side of the face became numb. In addition, blisters in the erythematous area coalesced and formed ulcer-like appearance. The patient also noticed left ptosis and double vision and became unable to open the mouth, which made oral intake impossible. The patient was admitted to the hospital for deteriorated general condition with dehydration, severe pain and fever. On admission, the patient was found to have partial paralysis of the left 3 rd, 5th and 6th cranial nerves in addition to severe erythema with edema and small ulcers, covering the left side of the face and frontal region. The hydration treatment was initiated with 3 bags of 500 ml glucose and electrolyte solution and continued for 6 days with a decreasing dose during the hospitalization. Initially, two bags of these solutions (500 ml) had been enriched with molecular hydrogen H2. No antibiotic was given. Before the infusion therapy, the patient was unable to open his left eye and the mouth (Figure 1, upper left). The picture of Figure 1 upper right was taken after the patient was asked to open his left eye and the mouth. The patient was unable to do so, except for minimal opening of the mouth. However, 3 days after the admission and molecular hydrogen H2 infusion, the patient’s condition remarkably improved, including erythema, ulcers, pain level, opening the eye and mouth (Figure 1, lower left) and the patient became afebrile. Since cranial nerve functions recovered also and he became able to take oral soft nutrients, intravenous hydration was decreased to 2 bags of molecular hydrogen H2- enriched glucose-electrolyte solution (esuron B,200 ml/bag), daily. By the 6th hospital day, the patient was eating a regular food and his dehydration was corrected. He had no pain and the severe inflammation of the skin disappeared. The patient discharged home and no return of the skin erythema noted during a follow-up period (Figure 1, lower right).
67 y.o male lapsed into coma after a large basilar artery aneurysm rupture and subarachnoid hemorrhage. After the aneurysm was surgically clipped, the patient remained comatose and developed pneumonia and cystitis, with deterioration of the liver and kidney function. After multiple medications including antibiotic and anticonvulsant, his general condition had been stabilized until 2 months after the surgery when he became febrile and developed severe skin abnormality. The abnormality consisted of erythematous papules, severe skin edema, blisters and vesicles and shedding of the skin. The Stevens-Johnson syndrome was suspected and he was transported to a general hospital with dermatology department. However, the patient was sent back with several diagnosis such as drug erythema, thrombocytopenia, possible trichophyton infection etc. and use of steroid and antifungal cream were recommended but not systemic steroid. However, application of these creams further deteriorated the skin condition despite of discontinuation of suspected drugs and finally, it was decided to use molecular hydrogen H2-enriched intravenous fluid. After a complete PARQ with the patient’s family who signed a consent,molecular hydrogen H2-enriched saline solution (500 ml) was given twice a day. Redness of the skin started fading and swelling and hardness of the skin from severe edema significantly improved in 3 days. His high fever subsided. After one week of the hydrogen treatment, the skin lesions almost disappeared (Figure 2, lower left) and general condition improved also. Although the patient remained comatose after the treatment and expired approximately 4 months after the surgery, the skin lesions did not recur.
48 y.o female started feeling hot sensation in her face and developed erythema in the entire face (Figure 2, upper left) after a CT scan study with contrast enhancement for cerebral aneurysm. Drug eruption was suspected and a minophagenC solution (Minophagen Pharmaceutical Co.) which had been effective in these situations, was given intravenously. However, the erythema did not subside and the patient developed fever (38.5○C), headaches and nausea. As an emergency measure, two bags of a 250 ml of saline solution (Terumo Co.), which had been enriched with molecular hydrogen H2 was given. Approximately 30 min. after the infusion, the erythema started fading in the left side of the face first (Figure 2, upper middle) and then in about one hour, the whole face improved (Figure 2, upper right) and her body temperature started coming down in about one hour. At that point, the infusion stopped and the patient returned home. No recurrence of the skin rush nor fever was noted during a follow-up period.
62 y.o. male had been intubated and mechanically ventilated with stable vital signs after severe subarachnoid hemorrhage from a ruptured cerebral aneurysm until 7 days after the ictus when the patient developed high fever and erythema which consisted of finer papules without fusing together. Initially, the patient was treated with local ointments with steroid but the erythema spread in the whole body and started coalescing (Figure 2, lower middle). In 3 days after molecular hydrogen H2-enriched saline solution was given twice a day intravenously, the skin lesion started fading (Figure 2, lower right) and the elevated body temperature normalized.
Two volunteers who were already in Nishijima hospital with different medical conditions agreed to let the study to use molecular hydrogen H2 and their arterial access port and venous port which had been established for their medical treatment. The blood samples (1 ml at each time) were withdrawn from these ports, before, during and after molecular hydrogen H2 administration by intravenous infusion of 500 cm3 of saline or by inhalation of 2% molecular hydrogen H2 gas for 20 min followed by inhalation of 4% H2 gas. Both patients and their family understood perfectly that the study will not provide any benefit to them directly but possibly for the future of molecular hydrogen H2 treatment research. All the proper PARQ and signing of the consent form had been done before the initiation of the study.
Erythema of these 4 patients and associated symptoms, such as intensive pain in the face with neurological deficits and skin ulcers (case 1), fever and edematous hardening of the entire body, particularly in the extremities with skin ulcers (Case 2), rather mild but with acute fever and nausea and headache (case 3), mild but worsening and spreading skin lesions with fever (case 4), all improved significantly after the molecular hydrogen H2 treatment and did not recur.
The molecular hydrogen H2 delivery study of two volunteers showed that the concentration of molecular hydrogen H2 in the blood rapidly increased with molecular hydrogen H2 inhalation and slowly decreased with cessation of molecular hydrogen H2, particularly in the venous blood. However, molecular hydrogen H2 concentration of the air samples in the plastic bag covering a leg showed much slower changes and continued to increase even after molecular hydrogen H2 inhalation was discontinued, at least during the time of sample collection (Figure 5). The blood level of molecular hydrogen H2 was significantly higher when molecular hydrogen H2 was given by inhalation as compared to via intravenous route.
Administration of molecular hydrogen H2 did not change physiological parameters and did not cause significant deterioration of the blood chemistry, although some of these patients already had severe abnormalities before the molecular hydrogen H2 treatment such as thrombocytopenia of case 2
The safety monitoring with physiological parameters and laboratory studies showed no ill effects on those multiple indices and organ function such as kidney and liver function, by this method of molecular hydrogen H2 administration (Table 1). Even in the case 2 with thrombocytopenia, no other hematological worsening was noted. Clinical symptoms of the skin diseases of all four patients improved rather rapidly and significantly. Therefore, it may be reasonable to assume that molecular hydrogen H2 infusion in these situations was quite safe and effective.
In summary, erythema of these 4 patients and associated symptoms, such as intensive pain in the face with neurological deficits and skin ulcers, fever and edematous hardening of the entire body, rather mild but with acute fever and nausea and headache, mild but worsening and spreading skin lesions with red rush all improved significantly after the molecular hydrogen H2 treatment and did not recur.
The molecular hydrogen H2 delivery study of two volunteers showed that the concentration of molecular hydrogen H2 in the blood rapidly increased with molecular hydrogen H2 inhalation and slowly decreased with cessation of molecular hydrogen H2, particularly in the venous blood. However, molecular hydrogen H2 concentration of the air samples in the plastic bag covering a leg showed much slower changes and continued to increase even after molecular hydrogen H2 inhalation was discontinued, at least during the time of sample collection.
The blood level of molecular hydrogen H2 was significantly higher when molecular hydrogen H2 was given by inhalation as compared to via intravenous route.
complete article https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-14
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Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers
- Hirohisa Ono†Email author,
- Yoji Nishijima†,
- Naoto Adachi†,
- Masaki Sakamoto†,
- Yohei Kudo†,
- Jun Nakazawa†,
- Kumi Kaneko† and
- Atsunori Nakao†
© Ono et al.; licensee BioMed Central Ltd. 2012
Received: 25 December 2011
Accepted: 20 May 2012
Published: 20 May 2012
The authors would like to thank Miz Company for technical assistance for setting up the hydrogen water tank and initial measurement of H2 concentration in the intravenous fluid bag.
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© Ono et al.; licensee BioMed Central Ltd. 2012
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