Bronchial Asthma

Bronchial Asthma - the chronic inflammatory disease of the airway

Bronchial asthma is characterised by chronic airway inflammation, bronchial hyperreactivity and reversible airway obstruction (bronchoconstriction, mucosal oedema, increased mucus production)

Status asthmaticus is a refractory state of acute severe asthma that does not respond to standard therapy

2. Asthma is more common in children but there has been a rapid increase in adult-onset asthma lately. Males are more likely to affected than females.

3. Various trigger factors contribute to asthma.

Allergens - dust mites, pollen, dander

Bronchial infection

Cold air

Exercise

Drugs - aspirin, NSAIDs, beta-blockers

Emotions and stress

Various food

Hormones

Irritants - smoke, perfumes, smell, wood dust, etc

Extrinsic (allergic) asthma develops in patients who are prone to develop IgE antibodies.

Intrinsic (non-allergic) asthma is a manifestation in response to RTI or physosocial stressors.

4. The chief complaints are typically: cough, tightness, wheezing, dyspnoea. The symptoms often worsen at night which result in frequent awakening. If etiology is present, it worsens the symptoms. There is usually a medical history of allergies or atopies. Family history of asthma or other atopy must be noted.

Patients who smoke should be advised to stop smoking.

5. Physical examination is important to determine the severity of exacerbation. The patient may present with tachypnoea, tachycardia, usage of accessory muscles and pulsus paradoxus. On chest examination, there is hyperinflation of the chest, hunch shoulders and deformities - Harrison sulcus, pectus carinatum. Auscultation of the lungs - wheezing, prolonged expiratory phase

Be aware of dangerous signs of status asthmaticus such as paradoxical abdominal and diaphragmatic movements, pulsus paradoxus, altered mental status and silent chest (absence of wheezing). The patient may be also cyanotic and febrile. At a later stage there may be bradycardia and hypotension

6. The diagnosis of bronchial asthma is done via history taking, physical examination and confirmation through spirometry. A demonstration of reversibility more than 12% post-bronchodilator administration is diagnostic of asthma.

Pulse oximetry is monitored for oxygen saturation and supplemental oxygen given, aim to achieve >90% saturation.

Blood tests like FBC may reveal leukocytosis and eosinophilia.

Severe attacks of asthma, ABG may be needed to evaluate arterial pH levels, hypoxaemia and hypercarbia. In severe attacks, there is usually acidosis secondary to hypoventilation.

Chest X-rays are not recommended unless there is suspicion of complications.

Other tests that may be of help to identify trigger factors include bronchial provocation test and skin prick test.

7. The principles of management is to choose the treatment based on the severity. A stepwise approach to managing asthma is meant to assist decision-making.

In summary,

i. SABA prn

ii. + low dose ICS

iii. + low dose ICS and LABA

iv. + medium dse ICS and LABA

v. + high dose ICS and LABA

vi. + high dose ICS, LABA and oral corticosteroid

Consider monoclonal antibodies in step 5 and above if available (omalizumab)

Alternatives may be used in lower steps - theophylline, cromolyn

In children, leukotrine antagonists such as montelukast and zafirlukast is effective.

Patients are also educated on avoidance of trigger factors, warm-up exercise or SABA administration 5 minutes pre-exercise or LABA usage prior to exercise.

About one third of the patients fail to respond to treatment because of wrong technique. All patients should be re-educated on proper usage of and techniques.

8. Status asthmaticus is a medical emergency. Upon diagnosis of severe asthma,

i. oxygen supplementation 8L/min by mask is given to maintain SpO2 above 95%.

ii. high dose salbutamol or continuous nebulized 0.5% salbutamol

iii. IV prenisolone 250mg

iv. measure ABG, CXR for complications

v. if no improvement, IV MgSO4 25-100mg/kg over 20 minutes

vi. still no improvement, intubation with PPV

9. The complications of asthma include increased risk of influenza, pneumonia, pneumothroax, pneumomediastinum, COPD and iatrogenic Cushing syndrome.

Psoriasis and Psoriatic Arthritis

Psoriasis and Psoriatic Arthritis

Psoriasis is a chonic skin disorder characterised by excessive proliferation of keratinocytes resulting in formation of thickened scaly plaques, itching and inflammatory changes in epidermis and dermis.

Types: guttate, pustular, arthritis

2. There is a strong genetic component in the pathogenesis of psoriasis. Certain ethnicity such as Indians; HLA/MHC; Familial clustering; are associated with psoriasis.

Patients with celiac disease also have higher prevalence of psoriasis.

3. Psoriatic lesion is erythematous papule topped by loosely adherent scale.

Chronic plaques are symmetric, sharply demarcated, erythematous and silvery scale affecting the intergluteal folds, elbow, scalp, fingernails, toenails and knees.

Koebner's Phemomenon is the development of psoriatic lesion at traumatic sites (sunburn, scratch)

Auspitz sign may be demonstrated by scraping the scale which results in bleeding points.

Nail involvement is common - pitting nail plate, hyperkeratosis, onychodystrophy and onycholysis.

Patients often complain of variable pruritus, soreness and bleeding.

** The biggest impact of psoriasis is the psychosocial functioning of patients!

4. Guttate form occurs after streptococcal pharyngitis - multiple droplike lesions on the extremities and trunk.

5. Arthritic form is classified as seronegative spondyloarthritis and manifests as arthritis, dactylitis, spondylitis and enthesitis.

Arthritis is inflammatory in nature - symptoms of prolonged morning stiffness, joint erythema, warmth, swelling and joint effusion

Distribution of joint involvement: DIPJ type, symmetric type, asymmetric oligoarthritis, axial type and arthritis mutilans.

Dactylitis - diffuse swelling of digit
Enthesitis - inflammation at site of insertion of tendon into bone. Usually occurs at Archilles tendon-calcaneus. Manifests as swelling and tenderness.

Spondyloarthritis - sacroilitis, axial spine inflammation

Other manifestation - conjunctivitis and uveitis

6. Psoriasis is diagnosed clinically. Blood result and skin biopsy are rarely needed for confirnation.

Psoriatic Arthritis is diagnosed using Classification Criteria for Psoriatic Arthritis (CASPAR) - Score of 3 or higher is diagnostic

Thus laboratory workouts are tailored according to CASPAR. Acute phase reactants (ESR, CRP) is often raised. FBC may show anaemia of chronic illness. RF and ACPA is negative in 90% of the cases.

Radiological investigations of involved joints may show soft tissue swelling, joint space narrowing, subluxation, erosive changes. New bone formation such as periostitis and fusion may also occur. Digital erosive changes with adjacent heterotopic bone formation may result in "pencil in cup" deformity.

Other workouts if available include: identification of HLA B27, arthrocentesis to rule out crystal deposition disease and inflammatory synovial fluid.

7. Treatment of Psoriasis can be divided into non-pharmacological and pharmacological therapy:

Non-pharmacological therapy:
sunbathing
eliminating triggering factors
warm water bath and skin moisturisers
local hyperthermia
surgical taping or dressing

Pharmacological therapy:
topical steroids +/- aspirin cream
calcipotriene
tar product
anthralin
retinoids
oral PUVA (psoralen + exposure to UV)
methotrexate, cyclosporin, apremilast
TNF inhibitors

8. Treatment of Psoriatic Arthritis:
NSAIDs to alleviate symptoms in mild involvement
Intraarticular corticosteroid injections
DMARDs considered early in disease, if fail,
TNF inhibitors - infliximab, adalimumab, etanercept

Angioedema and Anaphylaxis

Angioedema - mucocutaneous swelling

Angioedema is the oedema of the deep layers of dermis and subcutaneous tissue. In comparison, urticaria involves the superficial dermis only. Angioedema is relatively common with 20% of the population ever experienced urticaria +/- angioedema during their lifetime.

2. Angioedema can occur with or without urticaria. It is classified into hereditary and acquired.

Hereditary angioedema is AD caused by C1 esterase inhibitor (C1-INH) defect (deficiency or mutation). The defect results in excessive protease accumulation which subsequently cleaves kininogen into bradykinin.

3. Acquired angioedema can be caused by a variety of aetiologies:
infection - HSV, Hep B, Coxsackie, Strep., parasites
Insect bites and stings
Physical, environmental and mental stress
CTS - SLE, HSP
Drugs - ACE inhibitors*, ARB (less), sulphur-containing drugs, aspirin, NSAID, phenytoin, rTPA
Food (antigen) - milk, egg, peanut, shellfish...

4. Mast cell activation and degranulation via type 1 hypersensitivity reaction or complement-mediated process results in the release of inflammatory mediators which leads to vascular leakage and oedema in deep layers of dermis and subcutaneous tissue.

5. Angioedema may be present as acute (<6w) or chronic (>6w).

The presentation of angioedema is non-pruritic, burning and not well dermacated. It can involve the eyelids, lips, tongue, extremities.

(To distinguish from urticaria - urticaria is pruritic, palpable, well dermacated and erythematous. It is smaller in size but multiple in number and usually fades 12-24 hours and frequently reappears at other sites.)

Further involvement may cause complications. Involvement of the upper airway (larynx) can cause respiratory distress while involvement of GIT system may lead to abdominal pain cyclic in nature and NVD.

It is often very DIFFICULT to determine the cause of angioedema. Patients should be asked regarding the aetiology exposure, drugs exposure, allergic history, as well as a family history of similar episodes (hereditary)

6. Diagnosis of angioedema is via detailed history and physical examination.

Laboratory testing is of limited value in diagnosis - it only helps in workup and evaluation. FBC, ESR and urinalysis may be ordered as initial evaluation of severity. C4 levels and C1-INH levels may be obtained if available in the hospital and would be reduced in hereditary form.

Stool ova and cyst, serology testing, skin prick tests may be done to determine the aetiology. Skin biopsy is reseved for chronic angioedema refractory to corticosteroid treatment.

7. The principle of management of angioedema is to eliminate the offending agent, avoid trigger factors and cold compression of affected areas. Since angioedema could present as emergency case of airway collapse, prompt actions must be taken.

8. Securing the ABC is of the upmost priority to ensure the airway remains patent.
High flow O2 is administered
IM/SC adrenaline 0.3-0.5 mg (1:1000 parts, care for risk of cardiac arrest).
IV fluid to be given if patient is hypotensive.
Antihistamine agents - H1 2nd gen (loratadine, cetrizine), H1 1st gen (diphenhydramine), H2 (cimetidine +/- ranitidine) given IV
Corticosteroids methylprednisolone given IV.

9. Hereditary angioedema may not respond to antihistamine agents. If cost is not an issue and C1-INH replacement therapy is available, it has been proven to be efficacious in treating acute attacks of hereditary angioedema.

10. Chronic angioedema is treated as per algorithm -
H1 second gen +/- H1 first gen +/- H2 +/- leukotrine receptor antagonist.
Prednisone is given at 1mg/kg/day for x5/7 then tapered down over few weeks.

11. Antihistamines usually provide symptomatic relief in 80% of patients with non-hereditary angioedema. Chronic angioedema may recur despite steroid treatment and can last for months and years.

12. The differential diagnosis include:
Urticaria
Anaphylaxis
Other skin disorders - cellulitis, dermatitis
Vasculitis

Steven-Johnson Syndrome and Toxic Epidermal Necrolysis

Steven-Johnson Syndrome (SJS) - the rare dermatological emergency with a prevalence of 1:100,000.

SJS is a vesiculobullous form of erythema multiforme affecting the skin, mouth, eyes and genitalia. Area of affected <10% - SJS; 10-30% - overlap syndrome; >30% Toxic Epidermal Necrolysis (TEN).

2. The aetiology is mainly drug reactions in supseptible HLA groups. The drugs mediate expression of various cytokines which trigger keratinocyte apoptosis and thus exfoliation of epidermis.

3. Some of the common medications known for causing SJS/TEN include:

anti-gout: allopurinol

antibiotics: cotrimoxazole, aminopenicillins, cephalosporins, quinolones, TMP-SFX

antiretrovirals

sulphur-containing drugs

phenytoin

phenobarbital

4. Patient presents with enlarging red-purple macules/papules/bullae at the conjunctiva, mucous membrane, nares and genital regions. The skin lesion enlarges within 2 days. There are flat, atypical target lesions or purpuric macules distributed on the trunk or widespread. The extent of involvement determines the classification of disease. Nikolsky sign (applying pressure on skin) may be positive with shearing off of epidermis.

5. Patient's history include cutaneous eruption that occurs within 8 weeks of drug initiation. Prior to the skin lesion, patient may complain of influenza-like symptoms (fever, cough, fatigue).

6. Delayed management may result in complications such as:

blindness due to corneal ulceration

haemorrhagic crusting at sites of stomatitis

dehydration due to poor oral intake (pain)

breathing difficulties due to thick mucopurulent sputum

difficulty urinating due to urethral involvement

7. Diagnosis is based on clinical presentation of the lesion. Laboratory tests are mainly to assess complications. A FBC and C+S may be ordered if suspected infection. Chest x-ray may show pulmonary involvement. If the diagnosis is uncertain, a skin biopsy may be performed. Serum electrolytes, urea, glucose, bicarbonate should be monitored to determine organ function and fluid balance.

8. The main principle of treatment is to WITHDRAW the drug and provide supportive care and management of secondary conditions. Referral should be made to ICU or burn unit. IVIG can be administered in severe cases. Recent studies by Paradisi A. et al (2014) suggest a role of TNF-a inhibitors (etanercept) to be efficacious in treating SJS/TEN. Other agents such as cyclosporine, cyclophosphamide and plasmapheresis may also be effective. Corticosteroids (prednisone) use is controversial due to risk of sepsis, but studies suggest that its usage is beneficial in early stages of disease.

9. Supportive treatments to improve QoL:

antihistamines to reduce pruritus

oral rinsing to relief oral lesions

provide soft diet and plenty of liquid for hydration

antibiotics cover if secondary infections

vitamin A to protect the eye against lacrimal hyposecretion

monitor the eyes for any worsening

catheterisation if urethral involvement

prophylactic anticoagulation

non-adhesive wound dressing

10. SCORETEN scale is used to predict the mortality risk and prognosis. The oral lesion may continue for several months. Permanent scarring and corneal abnormalities may occur in 20% of the patients. Late withdrawal of causative drug has a less favourable outcome.

11. The differential diagnosis include:

SJS-TEN spectrum

toxic erythema

pemphigus/pemphigoid

haemorrhagic fevers

staphylococcal scalded-skin syndrome