Terrible Disease Tuesday - TDT

TERRIBLE DISEASE TUESDAY (TDT)
CERVICAL CANCER
BY DR. NAOMI MULWENDO

INTRODUCTION
Cervical cancer is a type of cancer that occurs in the cells of the cervix which is the lower part of the uterus that connects to the va**na. It is the third most common type of cancer in women worldwide. Cervical cancer is the leading cause of cancer-related death for women in developing countries.
ETIOLOGY (CAUSE)
Various strains of the human papillomavirus (HPV), a s*xually transmitted infection, play a role in causing most cervical cancer. When exposed to HPV, the body's immune system typically prevents the virus from doing harm. In a small percentage of people, however, the virus survives for years, contributing to the process that causes some cervical cells to become cancer cells.
RISK FACTORS
• Many s*xual partners: The greater your number of s*xual partners — and the greater your partner's number of s*xual partners — the greater your chance of acquiring HPV.
• Early s*xual activity: Having s*x at an early age increases your risk of HPV infection.
• Other s*xually transmitted infections (STIs): Having other STIs — such as chlamydia, gonorrhea, syphilis and HIV/AIDS — increases your risk of HPV.
• A weakened immune system: You may be more likely to develop cervical cancer if your immune system is weakened by another health condition and you have HPV. Cervical cancer is five times more common in HIV infected women.
• Smoking: Smoking is associated with squamous cell cervical cancer.
• Exposure to miscarriage prevention drug: If your mother took a drug called diethylstilbestrol (DES) while pregnant, you may have an increased risk of a certain type of cervical cancer called clear cell adenocarcinoma.
• Use of combined oral contraceptives for 5 years or more.

CLINICAL FEATURES
The type of cervical cancer that you have helps determine your prognosis and treatment. The main types of cervical cancer are:
• Squamous cell carcinoma. This type of cervical cancer begins in the thin, flat cells (squamous cells) lining the outer part of the cervix, which projects into the va**na. Most cervical cancers are squamous cell carcinomas.
• Adenocarcinoma. This type of cervical cancer begins in the column-shaped glandular cells that line the cervical canal.
Generally, the early stages of cervical cancer are asymptomatic. Such individuals may be found with abnormal results on routine screening for the same.
The first symptom of cervical cancer is abnormal va**nal bleeding, usually after s*xual in*******se (postcoital). Other symptoms though uncommon include va**nal discomfort, malodorous va**nal discharge and discomfort or burning sensation when urinating (dysuria).
In later stages, cervical cancer extends and affects other body structures. The symptoms may differ depending on the affected part.
DIAGNOSIS
• Pap test - A Pap test can detect abnormal cells in the cervix, including cancer cells and cells that show changes that increase the risk of cervical cancer.
• HPV DNA test - The HPV DNA test involves testing cells collected from the cervix for infection with any of the types of HPV that are most likely to lead to cervical cancer.
• Punch biopsy - which involves using a sharp tool to pinch off small samples of cervical tissue.
• Endocervical curettage, which uses a small, spoon-shaped instrument (curet) or a thin brush to scrape a tissue sample from the cervix.
• Electrical wire loop, which uses a thin, low-voltage electrified wire to obtain a small tissue sample. Generally, this is done under local anaesthesia.
• Cone biopsy (conization), which is a procedure that allows to obtain deeper layers of cervical cells for laboratory testing. A cone biopsy may be done under general anaesthesia.
Staging exams include:
• Imaging tests such as X-ray, CT, MRI and positron emission tomography (PET). This help determine whether the cancer has spread beyond the cervix or not.
• Visual examination of the bladder and re**um.

TREATMENT
Treatment depends on several factors, such as the stage of the cancer, other present medical conditions, and patient’s preferences. Surgery, radiation, chemotherapy or a combination of the three may be used.
Surgery
Early-stage cervical cancer is typically treated with surgery.
Options include:
• Surgery to cut away the cancer only. For a very small cervical cancer, it might be possible to remove the cancer entirely with a cone biopsy. This procedure involves cutting away a cone-shaped piece of cervical tissue, but leaving the rest of the cervix intact. This option may make it possible for one to get pregnant in future.
• Surgery to remove the cervix (trachelectomy). Early-stage cervical cancer might be treated with a radical trachelectomy procedure, which removes the cervix and some surrounding tissue. The uterus remains after this procedure, so it may be possible to become pregnant.
• Surgery to remove the cervix and uterus (hysterectomy). Most early-stage cervical cancers are treated with a radical hysterectomy operation, which involves removing the cervix, uterus, part of the va**na and nearby lymph nodes. A hysterectomy can cure early-stage cervical cancer and prevent recurrence. But removing the uterus makes it impossible to become pregnant.
Minimally invasive hysterectomy, which involves making several small incisions in the abdomen rather than one large incision, may be an option for early-stage cervical cancer. People who undergo minimally invasive surgery tend to recover more quickly and spend less time in the hospital. But some research has found minimally invasive hysterectomy may be less effective than traditional hysterectomy.
Radiation
Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. Radiation therapy is often combined with chemotherapy as the primary treatment for locally advanced cervical cancers. It can also be used after surgery if there's an increased risk that the cancer will recur.
Radiation therapy can be given:
• Externally, by directing a radiation beam at the affected area of the body (external beam radiation therapy).
• Internally, by placing a device filled with radioactive material inside your va**na, usually for only a few minutes (brachytherapy).
• Both externally and internally
It should be noted that radiation therapy might cause menopause. Therefore, if one intends to get pregnant after radiation treatment, options about ways to preserve one’s eggs before treatment starts must be discussed with the attending physician.
Chemotherapy
Chemotherapy is a drug treatment that uses chemicals to kill cancer cells. It can be given through a vein (intravenously) or taken in pill form and sometimes both methods are used.
For locally advanced cervical cancer, low doses of chemotherapy are often combined with radiation therapy, since chemotherapy may enhance the effects of the radiation. Higher doses of chemotherapy might be recommended to help control symptoms of very advanced cancer.

Targeted therapy
Targeted drug treatments focus on specific weaknesses present within cancer cells. By blocking these weaknesses, targeted drug treatments can cause cancer cells to die. Targeted drug therapy is usually combined with chemotherapy and it might be an option for advanced cervical cancer.
Immunotherapy
Immunotherapy is a drug treatment that helps the immune system fight cancer. The body's disease-fighting immune system might not attack cancer because the cancer cells produce proteins that make them undetectable by the immune system cells. Immunotherapy works by interfering with that process. For cervical cancer, immunotherapy might be considered when the cancer is advanced and other treatments are not working.
Supportive (palliative) care
Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with the patient, the patient’s family and other doctors to provide an extra layer of support that complements the ongoing care. When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer.
Palliative care is provided by a team of doctors, nurses and other specially trained professionals. Palliative care teams aim to improve the quality of life for people with cancer or other debilitating illnesses and their families. This form of care is offered alongside curative or other treatments the patient may be receiving.
PREVENTION
• Vaccination. Receiving a vaccination to prevent HPV infection may reduce the risk of cervical cancer and other HPV-related cancers. This is currently given to girls (especially between 9 and 13 years old) that are not s*xually active.
• Routine screening tests. Pap tests can detect precancerous conditions of the cervix, so they can be monitored or treated in order to prevent cervical cancer. Mostly routine Pap tests can be done at age 21 or after one is s*xually active and repeating them every few years as directed by the attending physician. Other screening tests that can be done include Visual Inspection with acetic acid (VIA).
• Practice safe s*x. This reduces the risk of cervical cancer by taking measures to prevent s*xually transmitted infections and limiting the number of s*xual partners.
• Avoid smoking. To***co has been seen to contain carcinogens that predispose individuals to not only cervical cancer but many others.
REFERENCES
Cervical cancer (who.int)
Cervical cancer - Symptoms and causes - Mayo Clinic
Feather, D. Randall, M. Waterhouse, (2020). Kumar & Clark’s Clinical Medicine 10th Edition. Elsevier, UK.
https://www.cancer.org/cancer/cervical-cancer.html
Konar H. (2013). Dc Dutta’s gynecology including Contraception. 6th Edition. Jaypee brothers medical publishers (p) Ltd. India.

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TERRIBLE DISEASE TUESDAY (TDT)
PULMONARY TUBERCULOSIS (PTB)
BY SAMUEL CHILAWA (MEDICAL STUDENT)
21st AUGUST, 2021
INTRODUCTION
Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (MTB). It primarily affects the lungs (Pulmonary) but other organs can be affected. TB was identified as a contagious disease by Hippocrates (400 BC) and it was called phthisis, from the Greek word ‘phthinein’ (to waste away) because an infected individual would become wasted inevitably. TB is one of the world’s commonest infectious diseases as it is estimated that one-third of the world population is infected with tuberculosis, majority of cases (approximately 65%) are recorded in Africa and Asia (Feather, et al., 2020). TB was responsible for about 1.6 million deaths worldwide in 2017 and 20% of these were HIV co-infected individuals. Zambia has a TB prevalence of 376 per 100,000 population and it is ranked among the top 30 countries with the highest per capital burden of TB worldwide (MoH-Zambia, 2017).
ETIOLOGY (CAUSE)
MTB Comes from a large Mycobacteriaceae family. They are non-motile, non-capsulated and are strict aerobe (an organism which requires oxygen for growth). The cell wall for MTB is lipid rich with a mycolic acid which is a unique component. PTB is a disease of respiratory transmission (airborne), patients with active disease expel the bacilli into the air by coughing, sneezing or even shouting. Once inhaled, the bacilli are capable of implanting in the lungs and can spread to other parts of the body.
PREDISPOSING FACTORS
The risk factors for tuberculosis can be classified as follows according to (Feather, et al., 2020).
 Contact with risk groups: Originating from high incidence areas or frequent travel to high incidence areas.
 Immune deficiency: HIV infection, corticosteroids or immunosuppressant therapy, Nutritional deficiency, Diabetes Mellitus, chronic kidney disease, Malnutrition.
 Lifestyle factors: Alcohol misuse, Poor ventilation, Overcrowding,
 Others: Age (15 years)
PATHOPHYSIOLOGY.
Once the bacilli are inhaled, the macrophages (type of white blood cell) found in the lungs will engulf (completely surround) the bacilli. Ideally the macrophages are able to degrade pathogens (bacteria and microorganism capable of causing disease) but they fail to degrade MTB due to its mycolic layer, as well failure to create phagolysosomes. The Bacilli will persist in the macrophages and multiply. The macrophages will present the bacilli to another set of immune cells called T helper cells, these cells produce gamma interferon which activates the macrophages and enables them to become bactericidal (substance that kills bacteria). After a series of immune activities, a granuloma is produced which contains a central area of caseous necrosis, a unique form of cell death in which tissue maintains a cheese-like appearance. This is surrounded by giant cells, epithelioid cells, lymphocytes and macrophages enclosed in a fibrous tissue. Subsequently the central areas heal and become calcified (hardened), some of the calcified areas still contain the bacilli which are contained by the immune system and are capable of lying dormant for many years, known as latent TB. On initial contact with the infection, a few (less 5%) develop active disease. Majority of active TB cases are due to reactivation of latent TB, in which the initial infection was contacted many years ago. Extra pulmonary infection occurs by spreading via lymph nodes and the blood stream to distant sites such as the brain, bones, skin, etc.
CLINICAL FEATURES:
Pulmonary TB is presumed when a person is presenting with some or all of the following:
• Cough (Dry or productive) for 2 or more weeks.
• Chest pain
• Fever
• Hemoptysis (coughing up blood)
• Dyspnea (Difficulties in breathing)
• Other (nonspecific): Weight loss, loss of appetite, Drenching night sweats, malaise and weakness.
DIAGNOSIS:
To confirm the diagnosis of PTB, the following laboratory and imaging investigations can be done.
 Laboratory:
• Gene xpert for sputum
• Smear microscopy
• Sputum culture for mycobacterium.
• Other lab investigations include; Line probe assay, Lateral flow urine lipoarabinomannan (urine LAM), etc.
 Imaging:
• Chest radiograph: Important screening and diagnostic tool. Can be used to diagnose complications of TB such as pneumothorax, bronchiectasis, and fibrosis.
• Ultrasound: Aid to diagnose extra pulmonary TB affecting abdomen, pleura or pericardium.
• Computed tomography(CT) scam and magnetic resonance imaging (MRI).
 Supportive investigation: Full blood count, diagnostic counseling and testing (DCT), liver function test, liver biochemistry and renal function test.


TREATMENT:
The aims of TB treatment according to the Zambia National Tuberculosis and Leprosy Program (2017) are:
• To cure patient and restore quality of life and productivity
• To prevent death from active TB or its effects
• To prevent relapse of TB
• To reduce transmission to others
• To prevent the development and transmission of drug resistance
When a diagnosis of PTB is made, the recommended first line medications are Rifampicin, Isoniazid, Ethambutol and pyrazinamide. They are usually given in fixed dese combinations and not single drugs. The treatment period is divided into intensive phase (first 2 months) and continuation phase (can vary from 4 to 10 months depending on the severity of the disease). Dosages vary with body weight and should be taken as prescribed by your physician. Other medication may be included depending on the individual patient presentation and severity.
Direct observed therapy is used to ensure patient takes the right medicine, right doses and at the right intervals, the supervision is carried out a health worker or a community worker.
PREVENTION OF TUBERCULOSIS:
• Isolation of patients with active PTB
• Ventilate rooms/ Avoid overcrowding
• Mouth covering/ wear mask if you have active infection to prevent further spread
• Isoniazid preventive therapy for people living with HIV.
• Vaccination (BCG vaccine)-Given to children who are exposed or are in endemic areas.

References
T.E Herchline, M.S. Stuart. 2021. Tuberculosis. Medspace.

Feather, A., Randall, D. & Waterhouse, M., 2020. Kumar & Clark's Clinical Medicine. 10th Edition ed. London: ELSEVIER.

MoH-Zambia, 2017. National Tuberculosis and Leprosy Program. Tuberculosis Manual, Volume 5th Edition.

Ralston, S., Penman, I., Strachan, M. & Hobson, R., 2018. Davidson's principles and Practices of Medicine 23rd. 23rd ed. London: ELSEVIER.

TERRIBLE DISEASE TUESDAY (TDT)

ACUTE RHEUMATIC FEVER

BY VUNZYA P. NSOKOLO (MEDICAL STUDENT)

10TH AUGUST, 2021

DEFINITION

Acute Rheumatic Fever is an auto-inflammatory disease of the heart, joints, skin and the basal ganglia of the brain (specifically the corpus striatum) that results from infection with bacteria belonging to Lancefield Group A beta hemolytic streptococcus (GAS). Acute Rheumatic fever is always preceded by pharyngitis (Inflammation of the Pharynx), commonly known as sore throat, about 2-3 weeks prior to its onset.

ETIOLOGY (CAUSE)

Acute rheumatic fever is caused by Streptococcus pyogenes (group A hemolytic streptococcus). Streptococci are Gram-positive, nontitle, catalase-negative, facultative anaerobic cocci that occur in chains or pairs. Their classification is based on their hemolytic ability on blood agar culture medium and the antigenicity of a carbohydrate in the cell wall (Lancefield antigen).

EPIDEMIOLOGY

It is common in the Middle and Far East, Eastern Europe and South America. It is rare in the UK, Western Europe and North America. This decline in the incidence of rheumatic fever (from 10% of children in the 1920s to 0.01% today) parallels the reduction in all streptococcal infections and is largely due to improved hygiene and the use of antibiotics. The annual incidence of acute rheumatic fever in some developing countries exceeds 50 per 100,000 children. Acute rheumatic fever incidence peaks in children of ages 5-15 years as this is the age range at which the risk of streptococcal pharyngitis is highest.

PATHOPHYSIOLOGY

The pathogenicity of group A streptococcus is conferred by a variety of extracellular proteins and toxins. These include streptolysin O and S (which are toxic to living cells), Streptokinase and Hyaluronidase, among others. Upon infection, the body mounts an immune response that leads to the pharyngitis. This involves recognition of the pathogen associated molecular patterns (PAMPs) by cells of the innate immune system (macrophages, Natural killer cells, dendritic cells). This leads to phagocytosis (ingestions of bacteria by cells of the immune system), elicitation of pro-inflammatory mediators and subsequent presentation of these pathogens to the lymphocytes in regional lymph nodes that elicit an antigen specific response that involves antibodies (Antigen: A substance which the body recognizes as foreign, Antibody: A blood protein produced by the body to in response to and counteracting an antigen). Because of a phenomenon known as molecular mimicry (Structural and functional similarities shared between molecules found in infectious pathogens and the host), these antibodies against streptococcus attack host tissues leading to inflammatory processes in these tissues. This is because certain pathogenic streptococcal components such as M proteins and other cell wall and cell membrane components mimic or exhibit similarity in epitopes (antigenic patterns) with host cells such as those of the heart, skin and basal ganglia.

CLINICAL FEATURES

The clinical presentations of acute rheumatic fever are what form the basis of the Jones diagnostic criteria. These are:
• Pancarditis (inflammation of the heart)
• Sydenham's chorea (St. Vitus' dance), dance like movements of the head
• Migratory polyarthritis
• Erythema maginatum (rash with red margin)
• Subcutaneous nodules
• Fever
• Malaise
• Arthralgia (joint pain).

DIAGNOSIS

Diagnosis is guided by the Jones Criteria along with laboratory investigations.

(a) Jones criteria is a diagnostic criteria for acute rheumatic fever which consists of 5 major criteria and 4 minor criteria, with the requirement of evidence of a preceding GAS infection either by positive throat culture, elevated Anti-streptolysin O titer (ASOT) or history of pharyngitis in the preceding 2-3 weeks.

Major criteria

(i) Pancarditis- Active inflammation of the myocardium, pericardium, and endocardium to varying degrees. This may manifest with breathlessness, chest pain, tachycardia, cardiomegaly or murmurs (soft systolic murmur due to mitral regurgitation or soft mid-diastolic murmur).
(ii) Sydenham's chorea: Purposeless, involuntary movements of hands, feet and face.
(iii) Migratory Polyarthritis: Inflammation of different large joints in quick succession and is characteristically responsive to aspirin
(iv) Erythema maginatum: Erythematous (superficial reddening of skin) macular lesions occurring on the trunk and proximal extremities but not on the face.
(v) Subcutaneous nodules: firm nodules on extensor surfaces.

Minor criteria

May be clinical or laboratory :
• Fever and arthralgia are clinical
• Prolonged P-R interval and tachycardia on ECG, elevated Erythrocyte Sedimentation Rate (ESR) and increased C-reactive protein are laboratory.

NOTE: Diagnosis is made in the presence of atleast 2 major criteria or 1 major with 2 minor criteria; with both these conditions being backed by evidence of previous GAS infection.

LABORATORY INVESTIGATIONS

• Throat swab and bacterial culture
• Antistreptolysin O titer (ASOT)
• Electrocardiography (ECG)
• Chest X-Ray
• Echocardiogram (Echo)

Differential Diagnosis:

• Juvenile Idiopathic arthritis
• Rheumatoid Arthritis

TREATMENT AND MANAGEMENT

• Bed rest
• Antibiotics: Single dose benzyl Penicillin or oral phenoxymethylpenicillin for 10 days to eliminate any residual streptococcal infection.
• Symptomatic: treat cardiac failure; Corticosteroids (prednisolone 2mg/kg/day in four divided doses) or aspirin for the carditis and arthritis.
• Chorea is minimized with minimal physical or emotional stress, with severe form being treated with haloperidol, chlorpromazine or diazepam.

PREVENTION: Secondary prevention of recurrent infections is conferred by prophylaxis with monthly IM Benzyl Penicillin where compliance is a possible challenge or Oral phenoxymethyl penicillin daily for 5 years

REFERENCES

Kumar, P., Clark, M. (2012). Kumar and Clark's Clinical Medicine. 8th edition. Elsevier. Edinburgh

Kayser, F.H., Bienz, K.A., Eckert, J., Zinkernagel, R.M. Medical Microbiology. Thieme. New York

Behrman.R., (2016). Nelson Textbook of Paediatrics, 20th Edition. Saunders. Philadelphia

Walker, B.R., Colledge, N.R., Ralston, S.H., Penman, I.D. (2016) Davidson's principles and practices of medicine. 22nd edition. Churchill-Livingstone-Elsevier. Edinburgh

Picture: Signs of Rheumatic fever

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TERRIBLE DISEASE TUESDAY (TDT)

PREMENSTRUAL SYNDROME (PMS)

BY SH*TULUKA MUSAKANYA (MEDICAL STUDENT)

27th JULY, 2021

INTRODUCTION

Premenstrual syndrome (PMS) is a group of symptoms that occur during the luteal phase of a woman’s menstrual cycle and lasts a few days after the onset of menstruation. The luteal phase is the period between ovulation and the onset of menstruation.

This syndrome usually affects 85-90% of women of the reproductive age and symptoms resolve after menopause. Women usually experience mild symptoms which range from behavioural changes to somatic changes. A small percentage of women do however experience severe symptoms that are sufficient to be classified under premenstrual dysphoric disorder (PMDD). PMMD is a severe form of PMS. Most women don’t take any medications because their symptoms are mild and do not disrupt normal physical activity but in a case where symptoms are severe enough some drugs can be taken.

PROPOSED RISK FACTORS

• Age: majority of patients are in the mid-20s to late-30s age group
• Stress
• Genetic predisposition
• Mental health problems like depression
• Obesity: body mass index >30

PATHOPHYSIOLOGY

The pathophysiology of premenstrual syndrome has not been fully understood. However, there are some theories that have been postulated. One theory has been attributed to the hormonal changes that occur during the menstrual cycle and the other to the 2 neurotransmitters systems, the GABAergic and the serotonergic systems which have been implicated in the development of PMS symptoms. The symptoms can occur during the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormones.

In the past generations, concurrent pregnancies, lactation and malnourishment in women resulted in extended periods of amenorrhoea, a situation which has been amended by improved nutrition and the use of contraceptives. Thus, women nowadays have much longer periods of cyclic fluctuations of oestrogen and progesterone with associated premenstrual symptoms. Since the most characteristic feature of PMS is the relation between symptom appearance and menstrual cyclicity, researchers have proposed that gonadal steroids (hormones) are involved in the pathophysiology. Women with and without PMS do not differ with respect to the production of s*x hormones, suggesting that PMS might be associated with enhanced responsiveness to normal, fluctuating concentrations of these hormones rather than their production (Yonkers et al, 2011).

Metabolites of progesterone formed by the corpus luteum of the o***y and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. S*x steroids have been shown to modulate serotonin transmission in rodent and non-human primates, indicating that gonadal hormones influence behaviour by interacting with serotonergic transmission. The lowering of serotonin can give rise to PMS-like symptoms like mood swings and irritability.

SYMPTOMS

The symptoms can be broadly grouped into two main group; somatic and behavioural.

Somatic symptoms include:

• Breast tenderness and swollenness
• Constipation or diarrhoea
• Bloating
• Abdominal pain
• Headache
• Lower backache
• Acne
• Lower tolerance to noise or light

Behavioural symptoms include:

• Irritability
• Change in circadian rhythm (sleep pattern)
• Nausea
• Appetite changes and food cravings
• Memory loss or trouble concentrating
• Anxiety and fatigue
• Mood swings
• Loss of interest in usual activities

DIAGNOSIS

• The diagnosis is mainly clinical and is derived from the history the patient gives.
• There are no unique physical or lab tests that diagnose premenstrual syndrome. The diagnosis requires daily charting of symptoms over two menstrual cycles: various methods have been developed for this purpose, such as the daily record of severity of symptoms. The patient records the day the symptoms start and the day when they stop. The importance of recording these symptoms is that it enables a clear diagnostic distinction between PMS/PMDD and premenstrual exacerbation of an underlying psychiatric disorder.
• Many researchers believe that premenstrual headache, migraine and epilepsy should not should not be regarded as part of PMS, but as separate conditions.

TREATMENT

Non-pharmacological

• Physical exercises
• Healthy eating
• Restrict intake of alcohol and caffeine
• Psycho-education and support
• Relaxation techniques

Pharmacological

• Selective serotonin re-uptake inhibitors (SSRI’s): Citalopram, Fluoxetine, Paroxetine, Sertraline.
• Hormonal interventions:
1. GnRH agonists: temporarily turn off hormone production in the o***y e.g Leuprolide (Lupron Depot), Goserelin (Zoladex).
2. Oral contraceptives: They stop ovulation e.g combination birth control pill drospirenone and ethinyl estradiol (yaz).
• Non-steroidal anti-inflammatory drugs (NSAIDs): Ibuprofen, Naproxene, Mefenamic acid, Aspirin.
• Dopamine D2 receptor agonists like bromocriptine for mastalgia.

Alternative medicine

• Vitamin supplements: Vitamin B6 (pyridoxine), calcium, magnesium, vitamin E
• Herbal remedies: Some women report the relief of symptoms with the use of herbs such as ginger and evening primrose oil.
• Acupuncture

Note: Selective serotonin re-uptake inhibitors also exert some palliative effect on somatic symptoms.

It should also be noted that these drugs should not be self-prescribed. Please visit your nearest health facility when you develop these symptoms or consult your doctor.

REFERENCES

Gudipally P.R, Sharma G.K (2021) Premenstrual syndrome [online]. Available at https://www.ncbi.nlm.nih.gov/books/NBK560698/ (Accessed: 14 July 2021).

Johnson T.C (2020) Medications To Relieve The Symptoms of PMS [online]. Available at https://www.webmed.com/women/pms/medicine-for-pms (Accessed 14 July 2021).

Milewicz A, Jedrzejuk D (2006) Premenstrual syndrome: From etiology to treatment [online]. Available at https://www.sciencedirect.com/science/article/abs/pii/S0378512206002386 (Accessed: 13 July 2021).

Rapkin A.J, Akopians A.L (2012) Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder [online]. Available at https: //pubmed.ncbi.nlm.nih.gov/22611222/ (Accessed: 13 July 2021).

Yonkers K.N, O’Brien S.P.M, Eriksson E (2011) Premenstrual syndrome. National Institute of Health, USA.

Picture: A woman in agonizing lower abdominal pain due to premenstrual syndrome

TERRIBLE DISEASE TUESDAY (TDT)

BY MATIMBA MOLLY CHILALA (MEDICAL STUDENT)

20TH JULY, 2021

ANDROGEN INSENSITIVITY SYDROME (AIS)

DEFINITION

Androgen Insensitivity Syndrome (AIS), formally known as testicular feminisation, is an X-linked genetic disorder in which a foetus with 46 XY karyotype (genetic make-up) is unresponsive to the male hormones, the androgens (Gopalan, 2019). Androgens are hormones responsible for male secondary s*xual characteristics in males. Consequently, the affected individual portrays a female phenotype (physical characteristics) but with a male genotype (Medline, 2020).

This condition may manifest as Complete Androgen Insensitivity Syndrome (CAIS), characterised by typical external genitalia for females, or Partial Androgen Insensitivity Syndrome (PAIS), which is characterised by either predominantly female genitalia, predominantly male or ambiguous external genitalia (Trifiro & Trifiro, 2017). Mild androgen insensitivity syndrome is a less common form compared to the previously stated varieties.

EPIDEMIOLOGY

The average prevalence rate of complete androgen insensitivity syndrome has been approximated to occur in 2:100,000-5:100,000 for every genotypic male born. However, the prevalence rate of partial androgen insensitivity syndrome is approximately similar to that of CAIS (Trifiro & Trifiro, 2017).

ETIOLOGY (CAUSE)

Androgen insensitivity syndrome is caused by a mutation (alteration) in the androgen receptor (AR) gene encoding for androgen receptors, protein molecules that permit the entry of androgens into the cell. As a result, cells are deprived of androgens and cannot respond to them to achieve the desired outcome. Approximately two thirds of this condition are inherited maternally due to a mutation in the AR gene. The other one third results from a novel mutation occurring in the mother’s o**m before the child is conceived or during foetal development (Genetic Home Referencing, 2020).

SIGNS AND SYMPTOMS

Individuals with complete androgen insensitivity syndrome exhibit normal female external genitalia with the absence of internal genitalia such as the uterus, fallopian tubes and ovaries. Breasts usually develop normally.

Patients usually present at puberty due to other manifestations such as:

• Amenorrhea (absence of menstrual periods)
• Sparse or absent p***c hair
• Cryptorchidism, a condition in which one or both of te**es are undescended. The te**es remain in the abdominal cavity or in the inguinal canal. Descent of the te**es is dependent on the androgen, testosterone, during embryonic development.

Partial androgen insensitivity syndrome patients exhibit a spectrum of different signs and symptoms according to the severity. Some patients predominantly have female external genitalia with signs of external masculinisation and clitoromegaly (enlarged cl****is) or posterior labial fusion (Trifiro & Trifiro, 2017). PAIS patients with ambiguous or predominant male genitalia exhibit Reifenstein syndrome, a condition characterised by a triad of hypospadias, gynecomastia and a micro-p***s (Gopalan, 2019). These individuals develop sparse p***c hair at puberty.

The external genitalia of patients with mild androgen insensitivity syndrome are unambiguously male. Gynecomastia and under-masculinisation are evident at puberty. Sparse p***c hair and a micro-p***s also constitute this disorder.

DIAGNOSIS

Diagnosis of partial androgen insensitivity syndrome can be made at birth due to the appearance of the baby’s external genitalia. Nevertheless, complete androgen insensitivity syndrome can only be diagnosed later in life as the individual attains puberty. Patients with CAIS can, infrequently, be diagnosed incidentally during evaluation of an inguinal hernia.

Some of the investigations that can be carried out include:

Chronic villus sampling (CVS) - a prenatal procedure in which cells are extracted from the placenta to test for genetic abnormalities in the foetus.

Amniocentesis- a prenatal procedure used to extract amniotic fluid for testing. It is done at 15-20 weeks of gestation.

Ultrasound scan- used to confirm the absence of internal female genitalia, i.e., the uterus, ovaries and fallopian tubes. It is also used to detect undescended te**es.

Blood tests - to check the s*x chromosomes, check for genetic faults in the X-chromosome and measure the concentration of androgens which is abnormally high in individuals with AIS (NHS, 2018).

DIFFERENTIAL DIAGNOSIS

Conditions that may present in a similar way to AIS include:

Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome- also called va**nal agenesis, is a congenital malformation affecting females in which the Mullerian duct fails to develop resulting in agenesis of the va**na and uterus with normal external genitalia (Kirsch, et al., 2018).

Hypospadias- a congenital malformation in males in which the urethral or***ce is located on the ventral aspect of the p***s

Under-masculinisation of the external genitalia and pubertal under-virilization- a spectrum of many clinical syndromes that have no association with androgen insensitivity syndrome.

Premature 46, XY foetuses

MANAGEMENT

One of the challenges faced by the attending physicians and parents of infants born with androgen insensitivity syndrome is assigning the s*x of the infant as the external genitalia may appear ambiguous.

Psychological counselling and support group programs must be implored for the both the patient and the caregivers. These programs are, specially, of benefit to the patient who may face an identity crisis.

Oestrogen replacement therapy, calcium and vitamin D supplements are recommended as these patients often have decreased bone density. Oestrogen is also given in an attempt to stimulate the development of female secondary s*xual characteristics, if the patient and parents decide to maintain the female identity.

Surgery for patients with cryptorchidism is recommended to remove the undescended te**es. Gonadectomy (surgical removal of the go**ds) can also be used remove unwanted genitalia according to the s*x the patient or parents opt to maintain. Mastectomy (surgical removal of the breasts) is also carried out in males with partial androgen insensitivity syndrome presenting with gynaecomastia.

COMPLICATIONS

Testicular cancer- in association with cryptorchidism

Osteoporosis- due to decreased bone density

Infertility

Psychological distress- as a result of the identity crisis experienced by patients (Singh & Ilyayeva, 2019).

REFERENCES

Genetic Home Referencing, 2020. Genetic Home Referencing. [Online] Available at: https://ghr.nlm.gov/condition/androgen-insensitivity-syndrome>inheritance

Gopalan, 2019. Medical Dictionary (offline), s.l.: cleanpng.

Kirsch, A. J., Carter, S. M., Gross, S. J. & Wu, C. Q., 2018. MayerRokitansky-Kuster-Hauser Syndrome. MedScape.

Medline, 2020. MedlinePlus. [Online]
Available at: https://medlineplus.gov/about/using/usingcontent/

Mendoza, N. & Motos, M. A., 2013. Androgen Insensitivity Syndrome. National Library of Medicine, Issue 1, pp. 1-5.

NHS, 2018. NHS. [Online] Available at: https://www.nhs.uk/conditions/androgen-insentivity-syndrome/diagnosis/

Singh, S. & Ilyayeva, S., 2019. Androgen insensitivity sydrome. Books.

Trifiro, G. B. & Trifiro, M. A., 2017. Androgen Insensitivity Syndrome. Books.