A Review on: Mycosis Fungoides

A classic form of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) is an uncommon cutaneous cancer. With 60% of CTCL cases in Europe, it is the most common subtype. [1] Two types of cutaneous mycoses are dermatophytosis and dermatomycoses. Dermatophytosis is caused by agents from the genera Epidermophyton spp., Microsporum spp., and Trichophyton spp. Dermatomycoses, on the other hand, are skin illnesses brought on by different fungi, most frequently Candida species. [2] Implantation mycoses and invasive fungal infections can result in substantial morbidity and mortality, whereas superficial fungal infections are easily treated [1,2]. Numerous illnesses in humans are brought on by fungal infections or mycoses. The severity of mycoses varies, ranging from superficial infections affecting the skin's stratum corneum to widespread infections affecting the brain, heart, lungs, liver, spleen, and kidneys. [3] Mycoses, another name for fungal diseases, can be categorised into classes according to how invasive they are. Cutaneous mycoses are mycoses that result in superficial infections of the skin, hair, and nails. Mycoses that infect deeper tissues by penetrating the dermis and epidermis are referred to as subcutaneous mycoses. Systemic mycoses are mycoses that spread throughout the body. [4]

HISTORY

Alibert gave the illness the term mycosis fungoides (MF) in 1829, which translates to "mushroom-like fungal disease." More than a century later, from 1938 until 1949, French dermatologist Albert Lézary published papers describing cutaneous "monster cells" and a strange ailment that caused erythroderma and "cellules monstrueuses."  French dermatologist Jean-Louis-Marc Alibert initially reported mycosis fungoides in 1806. [40] The term "mushroom-like fungal disease" (mycosis fungoides) is highly misleading. However, the illness is a kind of non-Hodgkin's lymphoma rather than a fungal infection. Alibert described the skin tumours of a severe case as resembling mushrooms, which is how it got its name. [42] Due to the disease's visual resemblance to the treponemal disease Yaws, also called Pian, Alibert named it Pian fungicides in 1814. [26]   

Types of Mycosis                         

1) Superficial fungal infections

• Ringworm(dermatophytosis)
• Onychomycosis
• Candidiasis
• Tinea versicolor

2) Subcutaneous fungal infections

• Sporotrichosis
• Chromoblastomycosis
• Eumycetoma

3) Deep fungal infections

• Histoplasmosis
• Coccidioidomycosis
• Blastomycosis
• Aspergillosis
• Candidal urinary tract infection
• Invasive candidiasis
• Pneumocystis pneumonia
• Mucormycosis
• Cryptococcosis

1. Superficial fungal infections: -Fungal infections on the surface Your skin, nails, and mucous membranes (such as your mouth, throat, or vagina) are all affected by superficial fungal infections. Superficial fungal infections include, for instance:

• Ringworm (dermatophytosis): -Ringworm is caused by a class of fungi called dermatophytes that feed on skin, hair, and nail cells. They can infect your hands (tinea manuum), scalp (tinea capitis), feet (tinea pedis/athlete's foot), groin and inner thighs (tinea cruris/jock itch), facial hair and surrounding skin (tinea barbae), and other body parts (tinea corporis).
• Onychomycosis. Your fingernails or toenails can become infected with a variety of fungi (onychomycosis). This may result in broken and discoloured nails.
• candidiasis. Infections of the skin and mucous membranes (mucocutaneous) caused by Candida (typically Candida albicans) are known as candidiasis. These include candidal intertrigo, esophageal candidiasis, vaginal yeast infections (vulvovaginitis), oral thrush, and certain kinds of nappy rash.
• Pityriasis versicolour and tinea versicolour: - Tinea versicolour, also known as pityriasis versicolour, is a skin discolouration caused by the fungus Malassezia. Fungal infections under the skin If fungus enters a cut or wound, usually from an injury sustained when dealing with plants (such as a thorn scratch), you may get a subcutaneous fungal infection. They result in skin problems such as rashes and ulcers.

2. Subcutaneous fungal infection: -Tropical and subtropical regions of the world have higher rates of subcutaneous fungal infections. Examples consist of:

• Sporotrichosis (rose gardener’s disease). Sporothrix fungus causes sporotrichosis. You can also get sporotrichosis in your lungs or other parts of your body.
• Chromoblastomycosis. Many different fungi can cause chromoblastomycosis. It can cause a long-lasting (chronic) skin infections. Rarely, it spreads to other parts of your body.
• Eumycetoma. Many different fungi can cause eumycetoma. Your feet are most frequently affected.

3. Deep fungal infections: -Other than the skin, deep fungal infections can occur in the lungs, blood, urinary system, or brain. Certain diseases are opportunistic, which means they often only infect those with compromised immune systems. Invasive or deep fungal diseases consist of:

• Histoplasmosis. The fungus that causes histoplasmosis, Histoplasma, can infect your brain, lungs, or other bodily regions. It is frequently seen in the lowlands of the Mississippi and Ohio rivers.
• Coccidioidomycosis: - Coccidioidomycosis, which is caused by the fungus Coccidioides, can infect your lungs and, in rare cases, spread to other parts of your body. Arizona and California are where it is most prevalent. blastomycosis. The fungus that causes blastomycosis, Blastomyces, frequently infects your skin, lungs, and bones. In rare cases, it can also infect your spinal cord and brain.
• Aspergillosis: -Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis are two of the lung illnesses that can be brought on by Aspergillus, the mould that causes aspergillosis. It can also develop into a fungus ball (aspergilloma) or infect other parts of your body.
• Candidal infection of the urinary tract. The majority of urinary tract infections (UTIs) are caused by bacteria, but others, like Candida, are brought on by yeast. invasive candidiasis. Invasive candidiasis is caused by a variety of Candida species. Your heart, blood (candidemia), brain, eyes (endophthalmitis), bones, and other bodily components may get infected.
• Pneumocystis pneumonia: -The fungus Pneumocystis jirovecii can infect your lungs and cause Pneumocystis jirovecii pneumonia (PJP).
• Mucormycosis. Mucormycosis is caused by a class of moulds known as mucormycetes. Mucormycetes can cause brain and sinus infections. (rhinocerebral mucormycosis), skin (cutaneous mucormycosis), intestines (gastrointestinal mucormycosis), lungs (pulmonary mucormycosis), or many bodily areas simultaneously (disseminated mucormycosis). 
• Cryptococcosis. Cryptococcosis is brought on by Cryptococcus neoformans and Cryptococcus gattii. They typically cause lung infections, but they can also cause brain and spinal cord infections (cryptococcal meningitis).

Sign and Symptoms  

There are multiple stages of skin changes associated with mycosis fungoides. Not everyone makes it through every stage. Some may happen concurrently. For many people, the first sign of disease in the early stage is a mycosis fungoides rash. Mycosis fungoides phases include:

• Premycotic phase: A scaly skin rash occurs. It appears on sections of your body not generally exposed to the sun, like your lower abdomen, thighs, butt and breasts (chest).
• Patch phase: The skin around the rash gets thin. It may be itchy and dry, like eczema.
• Phase of plaque: Your skin develops hard or tiny, elevated bumps.
• Phase of the tumour: Tumours develop on your skin as elevated patches that pierce deeper than plaques. Your thighs, groin, armpits, and the inside of your elbow are the most frequently affected areas. The tumours may become infected and form ulcers.

Sign/Symptoms

Signs of infections that are superficial or subcutaneous 

The following are signs of subcutaneous or superficial infections:

• redness, rash, pain, or itching in the afflicted area. cracked, thick, or discoloured nails. 
• White spots in the tongue or throat, taste loss, or pain during eating. a bump under your skin that is painless. 
• Fungal infection symptoms in the lungs 

 The following are signs of a fungal lung infection: 

• Sometimes you'll cough up blood.  
• exhaustion (tiredness).  
• warmth.  
• difficulty breathing.  
• sore muscles.
• joint aches.  
• an ache.  
• Sweat at night.

Causes

Different groups of fungus, each of which causes a particular kind of illness, are the source of fungal infections. 

• Dermatophytes: -The most frequent cause of superficial skin infections like ringworm, athlete's foot, and fungal nail infections is dermatophytes. These fungus thrive on skin, nails, and hair because they feed on keratin.
• Yeast: -Infections like oral thrush, vaginal candidiasis, and skin rashes in moist body folds are caused by yeasts, particularly Candida species. 
• Moulds: -In individuals with compromised immune systems, moulds like Aspergillus can migrate to other organs and cause more serious infections, particularly in the lungs.
• Other environmental fungi that can enter the body through inhalation or broken skin include Histoplasma, Cryptococcus, and Sporothrix. These fungi can be found in soil or decomposing material.

Pathophysiology of Mycosis

Almost two-thirds of cutaneous lymphomas are T cell lymphomas. CD4 positive is the most prevalent immunophenotype.

Clonal growth of CD4 cells that frequently lack typical T cell antigens like CD7, CD5, or CD2 occurs in mycosis fungoides.

Keratinocytes draw these cells to the skin.

Pautrier microabscesses are the result of the cells clustering around the Langerhan cells as they build up in the dermis. A portion of the cancerous cells make their way to the nearby lymph nodes before entering the bloodstream and circulating among other CLA-positive T cells. [13]

Prognosis and Prospects Typical Disease Progression

The stage at diagnosis and the efficacy of treatment have a significant impact on the prognosis for Mycosis Fungoides. The prognosis for early-stage disease is frequently better, and many patients have long-term remission.

Factors Affecting Prognosis

The following are important variables that affect the overall prognosis:

• Early Diagnosis: The likelihood of a successful course of treatment increases with the early detection of the illness.
• Treatment Adherence: Effective disease management depends on adhering to the recommended treatment regimen.

Treatment

• Psoralen plus ultraviolet A (PUVA therapy): - is the most often suggested first-line treatment for mycosis fungoides. [5] PUVA is a type of photochemotherapy in which the photosensitising medication psoralen is either topically or orally, and then the skin is exposed to ultraviolet light. [27]
• Additional treatment alternatives are frequently required in cases of advanced mycosis fungoides because systemic treatments frequently result in resistance. [28]
• Total skin electron beam therapy (TSEBT): -skin-directed therapies in conjunction with systemic medications are recommended instead of HN2 or UVB alone for patients with very symptomatic, generalised thicker plaques who require an immediate response. [29]
• Targeted therapy using monoclonal antibodies: These medications identify and eliminate cancer cells. If your body has not reacted to other systemic therapy, medical professionals may employ targeted therapy. Mogamulizumab-kpkc (POTELIGEO®) and brentuximab vedotin (Adcetris®) are examples of treatments.

Children

• Because different modalities have different safety profiles, treatment for mycosis fungoides in adults and children frequently varies. [15].

REFERENCES

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