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A furore over the misuse of corticosteroids and the resulting side effects was witnessed for the first time in history during the second wave of the novel coronavirus disease (COVID-19) pandemic in India.
This is despite the fact that this versatile class of medicines has been in use for nearly 70 years now.
Synthetic steroids first became known in 1939 when testosterone was successfully synthesised in Germany. They were initially used to treat depression and also widely administered to German soldiers during World War II.
A few years later, chemists Edward Kendall and Philip Hench from the United States and Tadeusz Reichstein from Poland described the hormones produced by adrenal glands as cortisols and received the Nobel Prize in Medicine for the discovery in 1950.
Their understanding led to the synthesis of the first corticosteroid, cortisone, which was used to manage rheumatoid arthritis in 1948 at the Mayo Clinic, US.
Over the years, corticosteroids have become an integral part of the medical system and have been particularly helpful in managing auto-immune disorders, a condition in which the body’s immune system mistakenly attacks its own healthy tissues.
In such conditions, the immune system triggers inflammation even in the absence of any invaders and causes damages to healthy tissues, such as those in the joints (rheumatoid arthritis) or in the skin (psoriasis). Corticosteroids help shut down these inflammatory processes and alleviate the condition.
Pulmonologists also prescribe steroids for short duration to contain asthma attacks and long-term routines to treat intestinal lung diseases, allergies, hypersensitive immunity disorders and the exacerbation of chronic obstructive pulmonary disease.
They can be effective in treating high-altitude pulmonary edema, a life-threatening condition caused by hypoxia in the mountains even without any infection.
Cancer treatment also includes a wide range of uses for steroids. Often, they are a part of the main treatment, especially with lymphoma (cancer of the lymphatic system, the body’s disease-fighting network) and multiple myeloma (cancer of plasma cells).
They aid in the management of nausea and vomiting, common side effects of chemotherapy and are also used before CT scans to reduce the patient’s chances of allergic reaction from the contrast dye used during the imaging.
“Additionally, steroids help ease cancer-related fatigue and relieve pain, improving the overall quality of life,” Nikita Mehra, associate professor of medical oncology at the Adyar Cancer Institute in Chennai, said.
Since the side effects of corticosteroids can be as serious as the ailments they are intended to treat, doctors have always prescribed them keeping in mind the delicate balance between benefit and risk.
Between benefit and risk
The seriousness of the side effects depends on the type of corticosteroid, potency of the dose and the duration and method of administration.
For instance, they tend to cause fewer complications when applied topically in case of skin ailments or inhaled for a shorter duration for asthma.
In contrast, oral doses of steroids and injected steroids are likely to cause serious side effects. They can lead to depression, insomnia, increased appetite, mood swings and weight gain even when taken for less than three months.
So doctors usually observe extreme caution when prescribing the dosage and duration of steroid medication. Alongside, care is taken to prevent, minimise and treat the complications.
“There is no fixed response or dosing for steroids. We monitor and alter. If we see that steroids are not working, we never increase the dose; we just stop it,” Able Lawrence, rheumatologist and immunologist at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, said.
While prescribing, doctors also have to be careful about the circadian rhythm — the sleep cycle. The immune system is not much alert while the body is at rest.
So, it is best to take steroids just before the body is to wake up and the immune system is going to be active again, he said, adding that steroids are most effective in small doses.
Since steroids disturb glucose metabolism and suppress the immune system, doctors closely monitor blood sugar levels and try to rule out the risks of other infections.
Several doctors, particularly oncologists, prescribe antifungal medications along with steroids. “If the steroids trigger a fungal infection in the lungs of a cancer patient, the chances of survival become really low,” Mehra said.
Readjusted for COVID-19
To ensure this delicate balance between benefit and risk during the fight against the COVID-19 pandemic, the World Health Organization (WHO) in its September 2020 guidelines, made two recommendations.
It said steroids should be used for the treatment of patients with critical and severe COVID-19 and that they should not be used for non-severe patients.
It qualified critical patients as those suffering from acute respiratory distress syndrome, sepsis, septic shock or other conditions that would normally require life-sustaining mechanisms like ventilators.
Severe patients, on the other hand, are those with oxygen saturation levels below 90 per cent in room air, a respiratory rate of more than 30 breaths per minute or those who show signs of severe respiratory distress.
The guidelines highlight that steroids are among a relatively small number of interventions available to COVID-19 patients that can potentially reduce health inequities during the pandemic, as most of the other measures are expensive and often in short supply.
WHO’s recommendations are based on the findings of eight randomised trials on 7,184 participants across several countries for 28 days.
The trials found that when treated without steroids, the mortality rate in critical patients was 415 deaths per 1,000 patients as opposed to 328 deaths when treated with steroids.
In the case of severe patients, the mortality rate gets reduced from 334 deaths per 1,000 without steroids to 267 deaths with steroids.
But the trend gets reversed in non-severe patients. The mortality rate is 176 per 1,000 non-severe patients when they are treated without steroids.
But the rate increases to 215 in the group treated with steroids. This could be simply because of the fact that the non-severe patients did not derive any benefit from steroids, which may have instead done them harm, the trials concluded.
The WHO guidelines are broadly mirrored in the Union health ministry’s guidelines, the “Clinical Management Protocol for COVID-19 (in adults)”, updated on May 24, 2021. They also suggest low doses of steroids in mild cases only if the symptoms persist beyond seven days.
Despite these facts, how did corticosteroids become the off-label home remedy during the second wave?
HISTORY OF ABUSESteroid abuse has been rampant in case of topical ointments and for eye conditionsWhile COVID-19 has put the spotlight on the abuse of corticosteroids, an analysis by Down To Earth showed that such abuse was not uncommon in the country. The bulk of the research on steroid abuse, however, revolves around its topical use to cure skin diseases as these medicines are easily available, sometimes even without a prescription. The illegal use of steroids is common in fairness creams and beauty products because of their skin whitening properties. “Long-term use of fairness creams with steroids can lead to thinning of the skin, which is a permanent damage. The skin of some of the patients becomes sensitive to all sorts of infections in the future,” Ananta Khurana, faculty member in the dermatology department of Ram Manohar Lohia Hospital in Delhi, said. In certain extreme cases, quacks administer intravenous steroids for skin infections too. “This impacts the general immunity,” she said. Dehradun-based dermatologist Molly Thomas said the abuse was particularly high in rural India. In 2016, she, along with five other researchers, studied 723 patients in rural Uttarakhand and found that 30 per cent of them had unknowingly misused steroids. The researchers recovered 70 brands of harmful steroid creams from the patients. Advice from pharmacists and local healers account for up to 78 per cent of the steroid misuse, Thomas wrote in the May 30, 2020 issue of BMJ Open. Steroid abuse is also common in cases of eye ailments. “Its overuse in treating ophthalmic problems often leads to glaucoma-induced blindness in children. These drugs, often sold over-the-counter as they are not properly labelled as steroids, give temporary relief but cause irreparable damage,” Harbans Lal, vice president, All India Ophthalmological Society, said. He explained that people commonly used steroids to treat conjunctivitis, which often deteriorated the condition. Rajetha Damisetty, head of the steroid abuse task force of the Indian Association of Dermatologists and Venereologists and Leprologists, blamed the government for the mess. “After much delay, the government in 2018 brought 14 types of topical steroids under the Schedule H category [under the Drugs and Cosmetics Rules, 1945], which means they can be sold only with a prescription. Still, a large number of patients suffer from diseases triggered by topical steroids as they can still be purchased without a prescription,” she said. The association’s website shows one in every four skin patients suffers from steroid abuse. Khurana said some of the responsibility should also be borne by the manufacturers. “In India, often when a skin cream is banned because of illegal steroid use, manufacturers re-launch the cream under a new name,” she said. “While labels do mention scientific name of the steroid, it is a tall order to expect lay consumers to understand the implications.” |
This was first published in the 1-15 August, 2021 edition of Down To Earth