IS IT A CASE OF GROSS MEDICAL NEGLIGENCE?EFFECTS OF USE OF CORTICOSTEROIDS ON COVID-19 PATIENTS


Introduction: Cases of mucormycosis are in rise in India which was never heard of before except in South Asia. The surge has taken up an offshoot and is mainly being discovered in patients who suffered from Covid-19.


The terms "black fungi" or "dematiaceous fungi" are practical tags that recall the early days of mycological classification. At the beginning of the 19th century the grouping of anamorphic fungi relied on characters that were easy to observe with minimal optical equipment, such as colour mycelial. Since these times, and till today, hyphomycetes producing olive-grey, brown or black pigment in their cell wall or conidia are classified as "dematiaceous fungi" (referring to the meanwhile obsolete genus Dematium, originally introduced for black, clumpy fungi). The dark pigments are presumed to be DHN-like (dihydroxynaphthalene) melanins, although biochemical and structural characterization has not always been achieved and may involve various precursor molecules.


It has now become clear that black fungi do not comprise a single phylogenetic lineage, but stem from divergent branches of the fungal tree of life. The lineages share production of melanin-like pigments, which has had profound evolutionary consequences for these groups. In human- and phytopathogenic fungi melanins are linked to increased virulence. Melanins also provide protection from a broad range of environmental stress conditions.


With their adaptive potential to uncommon habitats, black fungi have raised increasing interest of mycologists in medical sciences as well as in environmental ecology. It has become clear that a comprehensive understanding of black fungal evolution, ecology and functionality requires a synergic interdisciplinary approach, supported by a cooperative effort among specialists. A first step to bundle the interests in black fungi and to create a common forum was the foundation of a Working Group "Black Yeasts" under auspices of the International Society for Human and Animal Mycology (ISHAM). A small-scale meeting was held in Graz, Austria (May 30–June 1, 2006), and focused on the extremophilic ecology of black fungi. The growing interest in the topic was reflected in the second workshop held in Utrecht, The Netherlands (April 26–28, 2007), jointly with the ISHAM-affiliated Working Group on "Chromoblastomycosis", with 55 participants from 19 countries.

Recommendation by WHO: Understanding the recommendations:


Recommendation 1: We recommend systemic corticosteroids rather than no corticosteroids for the treatment of patients with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence)

Recommendation 2: We suggest not to use corticosteroids in the treatment of patients with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).

(Ref: Corticosteroid for Covid-19. Living guidance, 2nd September, 2020 by World Health Organization)


Systemic steroids treat conditions such as lupus and multiple sclerosis. While corticosteroids can be called steroids, they're not the same as anabolic steroids.

The class of medicines prescribed and used by the Doctors for controlling the patients from Covid-19 include drug which is Corticosteroid. One such drug which has been prescribed by Doctors is Methylprednisolone. Methylprednisolone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions.


What are the ultimate impacts of steroids on human body? It can never be ruled out and wisely said that Doctors while prescribing drugs more particularly Corticosteroid would not be aware of the impacts. Not only is it left to this extent. But the doctors have prescribed the Corticosteroid i.e. Methylprednesolone to patients who did not have signs of Covid-19 but prescribed this drug along with Fabiflu which is a normal drug for fever.


We thus divide the research in 3 segments

  • Corticosteroid Drug

  • Lupus

  • Mucromycosis

It is necessary to know here what actually is Corticosteroid drug and the consequences of Corticosteroid drug.

Corticosteroids: What Are They


What are corticosteroids?

Corticosteroids are a class of drug that lowers inflammation in the body. They also reduce immune system activity. Because corticosteroids ease swelling, itching, redness, and allergic reactions, doctors often prescribe them to help treat diseases like:

  • asthma

  • arthritis

  • lupus

  • allergies

Corticosteroids resemble cortisol, a hormone naturally produced by the body’s adrenal glands. The body needs cortisol to stay healthy. Cortisol is a major player in a wide range of processes in the body, including metabolism, immune response, and stress.


When are they prescribed?

Doctors prescribe corticosteroids for a number of reasons, including:

  • Addison’s disease. This occurs when your body doesn’t make enough cortisol. Corticosteroids can make up the difference.

  • Organ transplants. Corticosteroids help suppress the immune system and reduce the likelihood of organ rejection.

  • Inflammation. In cases when inflammation causes damage to important organs, corticosteroids can save lives. Inflammation occurs when the body’s white blood cells are mobilized to protect against infection and foreign substances.

  • Autoimmune diseases. Sometimes the immune system doesn’t work correctly, and people develop inflammatory conditions that cause damage instead of protection. Corticosteroids decrease the inflammation and prevent this damage. They also affect how white blood cells work and reduce the activity of the immune system.

They’re often used to treat these conditions as well:

  • asthma

  • hay fever

  • hives

  • chronic obstructive pulmonary disease (COPD)

  • lupus

  • inflammatory bowel disease

  • multiple sclerosis

Types of corticosteroids

Corticosteroids can be systemic or localized. Localized steroids target a specific part of the body. These can be applied through:

  • skin creams

  • eye drops

  • ear drops

  • inhalers to target the lungs

Systemic steroids move through the blood to assist more parts of the body. They can be delivered through oral medications, with an IV, or with a needle into a muscle.

Localized steroids are used to treat conditions like asthma and hives. Systemic steroids treat conditions such as lupus and multiple sclerosis.

While corticosteroids can be called steroids, they’re not the same as anabolic steroids. These are also called performance enhancers.

Common corticosteroids

There are a number of corticosteroids available. Some of the most common brand names include:

  • Aristocort (topical)

  • Decadron (oral)

  • Mometasone (inhaled)

  • Cotolone (injection)

What are the side effects?

Some side effects can occur with topical, inhaled, and injected steroids. However, most side effects come from oral steroids.

Side effects from inhaled corticosteroids can include:

  • cough

  • sore throat

  • difficulty speaking

  • minor nosebleeds

  • oral thrush

Topical corticosteroids can lead to thin skin, acne, and red skin lesions. When injected, they can cause:

  • loss of skin color

  • insomnia

  • high blood sugar

  • facial flushing

Side effects from oral steroids may include:

  • acne

  • blurred vision

  • water retention

  • increased appetite and weight gain

  • stomach irritation

  • difficulty sleeping

  • mood changes and mood swings

  • glaucoma

  • thin skin and easy bruising

  • high blood pressure

  • muscle weakness

  • increased growth of body hair

  • susceptibility to infection

  • worsening of diabetes

  • delayed wound healing

  • stomach ulcers

  • Cushing syndrome

  • osteoporosis

  • depression

  • stunted growth in children

Not everyone will develop side effects. The presence of side effects varies from person to person. High doses for long periods of time increases the likelihood of having side effects.


Interactions

Certain medical conditions may affect the use of this medication. Tell your doctor if you have any health conditions.

It’s particularly important to tell them if you have:

  • HIV or AIDS

  • herpes simplex infection of the eye

  • tuberculosis

  • stomach or intestinal problems

  • diabetes

  • glaucoma

  • high blood pressure

  • a fungal infection or any other infection

  • a disease of the heart, liver, thyroid, or kidney

  • have had a recent surgery or serious injury

Corticosteroids can also alter the effects of other medications. However, the likelihood of interactions happening with steroid sprays or injections is low.

Be careful what you eat when taking this medication, too. Certain steroids shouldn’t be taken with food, as interactions may occur. Avoid taking this drug with grapefruit juice. Tobacco and alcohol can also cause interactions with certain medications.


The bottom line

Corticosteroids are powerful anti-inflammatory medications that can treat diseases like asthma, arthritis, and lupus. They can come with some serious side effects.

Make sure to talk to your doctor about the pros and cons of corticosteroids, other conditions or diseases you have, and ways to minimize side effects.


EVERYTHING YOU NEED TO KNOW ABOUT LUPUS

Lupus is a chronic autoimmune condition that can cause inflammation throughout your body. However, it tends to primarily be a localized condition, so it’s not always systemic.


An autoimmune disease is a condition in which your body’s own immune system is responsible for the inflammation and breakdown of its own cells.

Many people with lupus experience a mild version of it, but it can become severe without proper treatment. Currently, there’s no known cure for lupus, so treatment focuses on easing symptoms and reducing inflammation.


Lupus symptoms

The symptoms of lupus can depend on the parts of your body affected. The inflammation seen in lupus can affect various organs and tissues in your body, including your:

  • joints

  • skin

  • heart

  • blood

  • lungs

  • brain

  • kidneys

Symptoms can vary, depending on the individual. They may be:

  • permanent

  • disappear suddenly

  • flare up occasionally

Although no two cases of lupus are the same, the most common symptoms and signs include:

  • high fever

  • fatigue

  • body aches

  • joint pain

  • rashes, including a butterfly rash on the face

  • skin lesions

  • shortness of breath

  • Sjogren’s syndrome, which includes chronic dry eyes and dry mouth

  • pericarditis and pleuritis (pleuritis), which both can cause chest pain

  • headaches

  • confusion

  • memory loss

The inflammation from lupus can also cause complications involving various organs, such as the:

  • kidneys

  • blood

  • lungs

Early symptoms

The symptoms of lupus typically start as you’re entering adulthood. This can be anywhere between your teens and into your 30s.

Some early signs include:

  • fatigue

  • fever

  • rash

  • swollen joints

  • dry mouth or dry eyes

  • hair loss, especially in patches, which is referred to as alopecia areata

  • problems with your lungs, kidneys, thyroid, or GI tract

These are similar to symptoms of other conditions, so experiencing them doesn’t necessarily mean that you have lupus. However, it’s important to make an appointment with your healthcare provider to discuss them.

Mucormycosis is a systemic fungal infection caused by members of the class Zygomycetes, order Mucorales. It is seen in patients debilitated by immune ormetabolic disorders.


The class Zygomycetes consists of a septate hyaline molds that reproduce by both sexual and asexual means. These fungi are ubiquitous in soil and decaying vegetation. Five genera in the order Mucorales are responsible for disease in humans: Rhizopus, Mucor, Absidia, andrarely, Saksenaea and Cunninghamella.

What is mucormycosis (zygomycosis)?


Mucormycosis (also called zygomycosis) is a rare infection caused by organisms that belong to a group of fungi called Mucoromycotina. At one time these fungi were called Zygomycota, but this scientific name has recently been changed. These fungi are typically found in the soil and in association with decaying organic matter, such as leaves, compost piles or rotten wood.


Who gets mucormycosis?

Mucormycosis is a rare infection. The infection is more common among people with weakened immune systems, but it can occur (rarely) in people who are otherwise healthy. Risk factors for developing mucormycosis include: •Uncontrolled diabetes

  • Cancer

  • Organ transplant

  • Neutropenia (low white blood cells)

  • Skin trauma (cuts, scrapes, punctures, or burns)

How does someone get mucormycosis?

There are two main types of infection that people can get, and these depend on the route of exposure. In the pulmonary or sinus form, exposure occurs by inhaling fungal spores from the environment. These spores can cause an infection to develop in the lungs, sinuses, eyes, and face, and in rare cases can spread to the central nervous system. In the cutaneous form, the fungus can enter the skin through cuts, scrapes, puncture wounds, or other forms of trauma to the skin. Mucormycosis is not contagious and does not spread from person to person.


What are the symptoms of mucormycosis?

The symptoms of mucormycosis depend on where in the body the fungus is growing. Mucormycosis most commonly affects the sinuses or lungs. Symptoms of sinus infections include fever, headache, and sinus pain. Lung infections with the fungus can cause fever and cough symptoms. Skin infections can develop after the fungus enters through a break in the skin due to surgery, burns, or trauma. A skin infection can look like blisters or ulcers, and the infected tissue may turn black. Other symptoms of a skin infection include fever, and tenderness, pain, heat, excessive redness, or swelling around a wound. If the infection is not treated quickly, the fungus can spread throughout the body.


How do I know if I have mucormycosis?

If you have symptoms of the infection, you should see your health care provider. A health care provider can diagnose mucormycosis by taking a sample of infected tissue and sending it to a laboratory. There, the sample will be examined under a microscope.


How is mucormycosis treated?

Mucormycosis needs to be treated with antifungal medication prescribed by a health care provider. These medications are given by mouth or through a vein. Skin infections with the fungus may require surgery to cut away the infected tissue.


(Ref: National Center for Emerging and Zoonotic Infectious Diseases, CDC, USA)

Patients contracting this infection uniformly suffer from predisposing con-ditions: acidosis, uncontrolled diabetes mellitus, leukemia, lymphoma, AIDS, severe malnourishment, severe burns, cytotoxic therapy, and immune suppression from corticosteroid use.1,2,4-8 It has also been observed in patients with chronic renal failure, liver problems, and dialysis patients on deferoxamine therapy. There are no known predispositions based on age, race, or sex. Most cases are acute surgical emergencies, though a few chronic, indolent forms have been reported with signs and symptoms developing over a 4-week period. The primary sites of invasion are the paranasal sinuses, lungs, skin, and the GI tract.


· Clinical symptoms, signs, and pathological findings are similar in mucormycosis, regardless of etiology. These fungi show a predilection for arterial invasion, causing extensive emboli and necrosis of surrounding tissues. Vein and lymphatic invasion can occur later in the course of the infection. The acidotic, hyperglycemic environment existing inpatients with ketoacidotic diabetes mellitus particularly favors the growth of Rhizopus. It is thought that diabetic and immuno compromised patients lack normal phagocytic activity on their nasal and or almucosal surfaces. This allows proliferation of fungus, which does not occur in people with intact phagocytic activity, and the fungus spreads via the blood vessels.


There are 5 forms of the disease:

  • Rhinocerebral: This is the most common form, usually seen in patients with ketoacidotic diabetes mellitus. This form presents with sinusitis, facial and eye pain, proptosis, progressing to signs of orbital structure involvement. Necrotic tissue can be seen on the nasal turbinates, septum, and palate. This may look like a black eschar.1,8 Intracranial involvement develops as the fungus progresses through either the ophthalmic artery, the superior fissure, or the cribiform plate.

  • Pulmonary-This is most frequently seen in patients with neutropenia, such as those with leukemia or lymphoma. This form presents with fever, dypsnea, and possible hemoptysis.

  • Gastro Intestinal tract- This form is seen in severely malnourished patients, particularly in kwashiorkor, and has been seen in patients with amoebic colitis and typhoid. The stomach, ileum, and colon are usually involved, mimicking intra-abdominal abcess.

  • Cutaneous- This form can follow minor trauma, insect bites, wounds, burns, and use of non-sterile dressings. Necrotic lesions occur on the epidermis that are painful and hardened, usually with a blackened central area. These lesions can progress into the dermis and even muscle.

  • Disseminated- Dissemination can occur, mainly from the pulmonary form, to the heart, brain, bones, kidney, and bladder. Dialysis patients on deferoxamine therapy are predisposed to this form.


Diagnosis- Rapid diagnosis and initiation of therapy is critical due to the acute, fulminate nature of the infection. Diagnosis of mucormycosis rests upon the presence of predisposing conditions, signs and symptoms of disease, observation of fungal elements of specific morphology in histological sections, and direct smears of material, and, to a lesser extent, culture results. There are no reliable serological methods for diagnosis at present. Direct examination in 10% KOH of scrapings from the upper turbinates, aspirated sinus material, sputum, and biopsy material can be valuable. The presence of thick-walled, aseptate, and refractile hyphae 6 to 15 μm in diameter, with some hyphae being swollen and distorted, is indicative of the presence of Mucorales fungi. The symptoms of mucormycosis depend on where in the body the fungus is growing. Contact your healthcare provider if you have symptoms that you think are related to mucormycosis.


Symptoms of rhinocerebral (sinus and brain) mucormycosis include:

  • One-sided facial swelling

  • Headache

  • Nasal or sinus congestion

  • Black lesions on nasal bridge or upper inside of mouth that quickly become more severe

  • Fever

Symptoms of pulmonary (lung) mucormycosis include:

  • Fever

  • Cough

  • Chest pain

  • Shortness of breath

Cutaneous (skin) mucormycosis can look like blisters or ulcers, and the infected area may turn black. Other symptoms include pain, warmth, excessive redness, or swelling around a wound. Symptoms of gastrointestinal mucormycosis include:

  • Abdominal pain

  • Nausea and vomiting

  • Gastrointestinal bleeding

Disseminated mucormycosis typically occurs in people who are already sick from other medical conditions, so it can be difficult to know which symptoms are related to mucormycosis. Patients with disseminated infection in the brain can develop mental status changes or coma.


Conclusion: Addressing a press conference on Saturday May 22, 2021, NITI Aayog member (health) Dr. VK Paul said the surge in cases of Mucormycosis can be attributed to disproportionate use of steroids in treatment of Covid-19 patients.[30] Despite the recommendation by WHO to use systemic steroid, Corticosteroid has been prescribed and administered, non-adherence to the guidelines of World Health Organization, thus giving rise to a new offshoot to the post Covid-19 treatment resulting in Black Fugus-Mucormycosis fungal infection cases. Can the probability be ruled out thus saying it’s not an aftermath of prescribing drugs which have side effects and are the doctors not aware of the impact and consequences of prescribing such drugs for treating Covid-19 patients?

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