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manifestations are also observed. Disease onset is usually slow with initial symptoms
being pain, swelling and stiffness. In the early stage of disease, metacarpophalangeal
and proximal interphalangeal joints of fingers, toes, thumb, and wrist are affected.
Elbow, shoulder, and knee joints are also affected. Morning stiffness from 30 minutes
to several hours is common and usually reflects the severity of inflammation of joints.
Few patients may also experience prominent myalgia, fatigue, low grade fever, weight
loss, and depression in the initial stage. Extra-articular symptoms may include
amyloidosis, carpal tunnel syndrome, scleritis, vasculitis; subcutaneous, pulmonary
or ocular nodules, pericarditis, and osteoporosis.
Non-pharmacological Management
All the patients suffering from rheumatoid arthritis should be educated regarding
pharmacological and non-pharmacological management. These empowered patients
can participate in therapy-related decisions. Occupational and physical therapy help
patients in preserving joint function, extending joint range of motion, and strengthening
joints and muscles through strengthening exercises. Use of assistive devices can help
the patients with joint deformities to minimize disabilities. Sometimes counseling for
stress management can also help.
Pharmacological Management
Following categories of drugs are useful in the treatment of rheumatoid arthritis.
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Glucocorticoids
• Disease modifying antirheumatic drugs (DMARDs)
• Biological therapies
NSAIDs: The analgesic and anti-inflammatory properties of these drugs give
symptomatic relief to the patients. COX-2 isomer of COX (cyclooxygenase) enzyme is
responsible for production of inflammatory prostaglandins. NSAIDs could be either
nonselective NSAIDs or selective COX-2 inhibitors. Ibuprofen, diclofenac and
naproxen are examples of NSAIDs.
Glucocorticoids: Glucocorticoids inhibit cytokine release and give rapid
relief of symptoms and decrease inflammation. They can be administered orally,
intramuscularly, or intra-articular route. Prednisolone is given orally while
triamcinolone and methylprednisolone are administered into inflamed joints through
intra-articular injections. Due to long term complications and adverse effects, use of
steroids must be limited to short term use in the initial stage only.
DMARDs: Disease modifying antirheumatic drugs (DMARDs) should be given in
early 3 months of diagnosis to reduce joint erosion. Choice of DMARD and its
combination with other drugs depends on relative efficacy, severity of disease,
convenience, monitoring requirement, patient’s comorbidities, cost, time period to
benefit, prescriber’s experience, success rate of drug, side effects, and patients’
adherence. Monotherapy with DMARD includes hydroxychloroquine, leflunomide,
methotrexate, minocycline or sulphasalazine. Examples of combination therapy are
methotrexate/hydroxychloroquine, methotrexate/sulfasalazine or methotrexate/
sulfasalazine/hydroxychloroquine.
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Biological therapies: It is an emerging drug category which include biological
DMARDs, that are copies of the original biological compound and demonstrate
similar efficacy and safety. They are genetically engineered monoclonal antibodies
which selectively target different parts of the inflammatory pathways. Normally they
target TNF-, interleukins, T cells, and B cells. Examples are adalimumab, etanercept,
golimumab, infliximab, tocilizumab, anakinra, abatacept and rituximab, etc.
KEY POINTS
• Rheumatoid arthritis and osteoarthritis affect joints and extra-articular organs.
• Age, genetic factors, hormones and stress are important factors for the development of RA
• Females are more prone to develop RA
• Treatment with NSAIDs with glucocorticoids and DMARDs are useful for RA
• Occupational or physical therapy is also beneficial along with pharmacotherapy
9.2 OSTEOARTHRITIS
Osteoarthritis is the most commonly found form of arthritis related to age. It is a
chronic disease that particularly affects people over the age of 65 years. It is a complex
disease involving bone, cartilage and synovium. Weightbearing joints like hip and
knee joints are more susceptible than non-weight bearing joints. It is a common reason
for total knee or hip replacement surgeries.
Aetiopathogenesis
Following factors leads to development of osteoarthritis
• Increasing age
• Gender
• Genetic constitution
• Obesity
• Previous injury
• Previous diseases such as rheumatoid arthritis or gout
• Neuropathic joint disease such as charcot joints
Development of osteoarthritis can be divided into four stages:
1. Initial repair
2. Early-stage osteoarthritis
3. Intermediate stage osteoarthritis
4. Late-stage osteoarthritis
1. Initial repair involves proliferation of chondrocytes synthesizing the extracellular
matrix of bone.
2. In the early stage of osteoarthritis degradation of the extracellular matrix occurs
as protease enzyme activity exceeds chondrocyte activity. It results in net
degradation and loss of articular cartilage.
3. Intermediate osteoarthritis is associated with failure of extracellular matrix
synthesis and increased protease activity leading to further increasing cartilage loss.
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4. In the late stage of osteoarthritis there will be complete loss of cartilage.
Osteophytes are found at the joint margins and there will be sclerosis of adjacent
bone. Deformity is also observed at this stage.
Clinical Manifestations
The most common symptoms of osteoarthritis are joint pain, reduced range of motion,
and joint stiffness after a period of inactivity. Joint stiffness generally lasts for less than
30 minutes after periods of inactivity, limits the range of motion, affects daily activities,
and may exaggerate in the winter season. Signs associated with osteoarthritis include
local tenderness and proliferation in bones, soft tissue swelling, crepitus, muscle
atrophy, and effusion.
Non-pharmacological Management
Non-pharmacological measures are an important and integral part of treatment to
achieve maximum benefits. It includes education, exercise, weight loss, and lifestyle
modification. Education, advice, and access to information produces positive
behavioral changes and promotes self-confidence. Aerobic exercise and strength
training programmes improve functional capacity in older adults. Weight loss should
be achieved by dietary modification and increased physical activity. Application of
heat or cold to the diseased joint improves range of motion, reduces pain, and
decreases muscle spasm. Patients with functional disability can use assistive devices
like canes, crutches, and walkers.
Surgery is reserved for patients who fail to respond to medical therapy and have
progressive limitations in daily activities. In joint replacement surgery, metal or plastic
prosthetic devices are inserted to replace diseased joint surfaces. After the joint
replacement surgery, patients achieve significant pain relief and functional restoration.
Pharmacological Management
Pharmacological therapy is symptomatic and does not modify the disease condition.
Simple analgesics like acetaminophen and nonsteroidal anti-inflammatory agents are
commonly used in the treatment of osteoarthritis. Ibuprofen, diclofenac, naproxen,
and celecoxib are the examples of NSAIDs. Apart from these, opioid analgesics like
tramadol, morphine, and methadone are also effective.
Comparison of rheumatoid arthritis and osteoarthritis is given in Table 9.1.
Table 9.1: Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA)
Characteristics RA OA
Speed of onset Rapid (weeks to months) Slow (years)
Gender prevalence 3:1 1:1
(women to men)
Usual age of onset 35–50 years More than 50 years
Joints affected Small joints of hands and feet Weightbearing joints like hip and
knee joint
Inflammation Local and systemic Non or minimal
Morning joint stiffness 60 mins or more Less than 30 mins
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131
KEY POINTS
• Osteoarthritis is mainly age related and mostly involves hip and knee joints
• Treatment with NSAIDs is useful for both RA and OA
• Symptomatic treatment with education, exercise, weight loss and lifestyle modification may be
useful.
• Joint replacement surgery can be suggested for the patients nonresponsive to the medical therapy
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10
Dermatology
10.1 PSORIASIS
Psoriasis is a chronic inflammatory disorder characterised by well-demarcated red
scaly plaques on the skin. The disease affects approximately 0.44 to 2.8% of the
population in India.
Aetiology
This disorder appears to have a genetic predisposition and is triggered by environmental
factors. Multiple genes are likely to influence disease susceptibility. The strongest
association is with HLA-CW*06. The various non-hereditary factors include infections
like streptococcal infections or HIV infection, drugs like lithium, beta-blockers,
antimalarials, NSAIDs, tetracyclines, and corticosteroid withdrawal; obesity, alcohol,
smoking, and emotional stress.
Pathophysiology
There is attraction and migration of inflammatory cells, especially neutrophils. An
inflammatory process is the primary cause of the disease. The epidermis is thickened
(acanthosis) with a thickened upper horny layer (hyperkeratosis), which is reflected
by thick scaly skin. These changes are due to cytokines released by T-lymphocytes
which initiate a dermal response to unidentified antigenic stimuli (keratinocyte
proteins) which leads to proliferation of keratocytes and inflammatory changes in the
epidermis and dermis. T cells, dendritic cells, and cytokines such as TNF alpha, IL-12,
and IL 23 all contribute to its pathogenesis.
Clinical Manifestations
Psoriatic lesions are commonly observed on the scalp, elbows, knees, trunk, and nails.
The primary lesion is an erythematous plaque covered with silvery scales. Psoriasis
can present in different clinical patterns. Some of the clinical types are:
• Chronic plaque psoriasis: This is the most prevalent type with pinkish-red scaly
plaques, especially on extensor surfaces such as elbows and knees. There is
involvement of the lower back, ears, and scalp as well.
• Guttate psoriasis: This variant looks like a raindrop and is commonly seen in
children and young adults. This generally appears over the trunk about 2 weeks
after a streptococcal sore throat. It resolves spontaneously, even without
treatment.
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133
• Flexural psoriasis: The lesions can occur in later life in the axillae, groin, submammary areas, and genitalia. These lesions tend to be red and glazed rather than
scaly.
• Erythrodermic or exfoliative psoriasis: This is a severe, life-threatening condition
that can occur due to eczema or psoriasis. There is widespread inflammation of the
skin, and the patients show dehydration, electrolyte imbalance, temperature
dysregulation, and serious secondary infection. This disorder requires immediate
hospital admission, medical supportive therapy, and topical or systemic treatment.
• Pustular psoriasis: There are widespread tiny pustules that are sterile collections
of inflammatory cells. The patient generally complains of fever and general malaise.
It can be localised to the palms or soles or be generalized. Generalized pustular
psoriasis may be life-threatening because of systemic infections or cardiovascular
or pulmonary complications. When the pustular psoriasis is confined to the hands
and feet, it is called palmoplantar psoriasis.
Pharmacological Management
Topical Therapy
Emollients and keratolytics: Emollients like mineral oils and paraffins in oil-in-water
emulsion hydrate the stratum corneum and prevent the increased transepidermal
loss of water observed in psoriasis. Keratolytics like salicylic acid promote the
desquamation of scales. It can be used with cytostatic agents like coal tar and
dithranol.
Vitamin D analogues: These inhibit keratinocyte differentiation and production;
the most commonly used is calcipotriol. These are used for mild, localised psoriasis in
the form of lotions, ointments, creams, or scalp treatments.
Steroids: Topical glucocorticoid preparations are used in acutely inflamed psoriasis
to reduce inflammation. These are easy to apply and are more acceptable to the
patients.
Phototherapy: This has an immunosuppressive effect on the skin and has been used
in the treatment of psoriasis for many years.
PUVA: Psoralens plus UVA light is used in the treatment of moderate to severe
psoriasis. Psoralens (e.g. 8-MOP methoxypsoralen and 5-MOP) are drugs that are
activated by long-wave UV light, which interferes with DNA synthesis and reduces
epidermal turnover. These are taken orally 2 hours before exposure to UVA light.
Systemic therapy: Systemic therapy is used in severe widespread psoriasis,
intolerant or rapidly relapsing after topical therapy and phototherapy.
Methotrexate: This is a folic acid antagonist used for moderate to severe psoriasis.
Its initial dose starts with 5 mg orally increasing up to 30 mg weekly. Acute toxicity
can cause myelosuppression or gastrointestinal bleeding. Hepatic fibrosis is another
long-term risk associated with methotrexate, and regular monitoring of liver function
is required.
Acitretin: This is a vitamin A derivative that inhibits epidermal proliferation and is
effective in chronic plaque psoriasis. The initial dose is 25–30 mg daily for 2–4 weeks,
which can be increased to 75 mg daily. Mucocutaneous side effects, hair loss, and
lethargy are common side effects.
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Cyclosporine: It is recommended for patients with severe psoriasis who are not
responding to conventional therapies due to its cost and toxicity. Adverse effects
include nephrotoxicity, hypertension, hepatotoxicity, neurologic disturbances,
hypertrichosis, and an increased incidence of lymphoma.
Hydroxyurea: It affects cell proliferation by inhibiting DNA. It has similar adverse
effects to methotrexate but has a low prevalence of hepatotoxicity. It shows a good
response in pustular psoriasis.
Biologic therapy: Biologics are drugs used to block specific molecular steps
important in immune-mediated diseases. They are given parenterally to patients with
severe psoriasis. Some examples of biologics used in psoriasis are etanercept,
infliximab, adalimumab, ustekinumab, and efalizumab.
KEY POINTS
• Psoriasis is a chronic inflammatory disorder characterised by well-demarcated red scaly plaques
on the skin.
• Psoriatic lesions are commonly observed on the scalp, elbows, knees, trunk, and nails.
• Psoralens plus UVA light is used in the treatment of moderate to severe psoriasis.
• Topical glucocorticoid preparations are used in acutely inflamed psoriasis to reduce inflammation.
10.2 SCABIES
Scabies is an itchy rash caused by the itch mite Sarcoptes scabiei var hominis. It is
commonly observed in children and young adults, but can affect any age group.
Aetiology
The causative parasite of scabies is the itch mite Sarcoptes scabiei var hominis. Scabies is
transmitted by direct skin-to-skin contact or indirectly by contact with contaminated
material (fomites).
Pathophysiology
The female itch mite burrows into the superficial layers of the skin in which the eggs
are deposited. Later on, it transforms into larvae, nymphs, and adults. Papules may
appear within 2 to 5 weeks after an infestation. These papules are tunnel-shaped or
comma-shaped, with a length ranging in size from a few millimetres to 1 centimetre.
Unhygienic conditions and social overcrowding encourage the spread of the
condition, which is characterised by intense itching, usually worse at night.
Clinical Manifestations
It manifests clinically as red, itchy papules which can occur anywhere on the skin, the most
common sites being the palms and soles, between the web spaces of fingers and toes,
around the wrists and axillae, around the nipples and umbilicus, and on the male genitalia.
Non-pharmacological Management
• All members of the family should get simultaneous treatment.
• Intimate clothing and bedding should be disinfected by boiling or steam.
• Education regarding personal hygiene.
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135
Pharmacological Management
Sulphur: It is one of the oldest remedies used in the treatment of scabies. It is irritating,
stains clothes, and has an unpleasant odour, so it has become obsolete. It is available
as a 5% ointment.
Benzyl benzoate: Because of its unpleasant odour, weak ovicidal action, and short
duration of action, it is not recommended very often. It is available as a 25%
emulsion.
Permethrin: It is available as a 5% application and is a highly effective scabicide.
Gamma benzene hexachloride: It is available as a 1% cream and is a highly effective
scabicide. It is applied all over the body below the neck in the form of a film which is
left over for 12 hours, after which the patient is given a bath.
Ivermectin: This anti-filarial drug is highly effective against scabies with an oral
single dose of 200 μg/kg.
Crotamiton: A 10% lotion or cream available is applied thrice at 24-hourly intervals,
followed by a bath.
KEY POINTS
• Scabies is an itchy rash caused by the itch mite Sarcoptes scabiei var hominis.
• It is transmitted by direct skin-to-skin contact or indirectly by contact with contaminated
material.
• Unhygienic conditions and social overcrowding encourage the spread of the condition.
10.3 ECZEMA
The terms “eczema” and “dermatitis” are used interchangeably and describe itchy,
erythematous skin with well-defined erythematous patches or papules.
Aetiology
Although the exact cause of eczema is unknown, the aetiology is a combination of
genetic, environmental, and immunological factors. Abnormalities in both immunologic
and pharmacophysiologic characteristics occur in such patients. It is observed that
there is a frequent association of atopic dermatitis with other allergic disorders and
elevation of serum immunoglobulin E (IgE). Pharmacophysiologic abnormalities
include altered adrenergic and cholinergic responses.
Pathogenesis
Acute eczema is an inflammatory process leading to oedema in the epidermis, which
leads to intraepidermal vesicles. In eczema, the barrier function of the skin due to the
tightly-packed keratinocyte cells in the epidermis, which prevents the loss of
transepidermal fluid and the entry of pathogens, is lost.
In chronic eczema, prolonged rubbing and scratching results in a thickened
epidermis and an increase in the upper horny cell layer of keratin called hyperkeratosis.
Both acute and chronic stages are accompanied by a chronic inflammatory cell
infiltration of the dermis and epidermis, which leads to itching.
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Clinical Manifestations
Various clinical types are:
Atopic eczema: This affects up to 20% of children and up to 3% of adults; recent data
shows that its prevalence is still increasing, especially in low-income countries. Atopic
eczema typically manifests early in life and often precedes other allergic diseases such
as asthma or allergic rhinitis.
It presents as itchy erythematous scaly patches, especially in the flexures such as in
front of the elbows and ankles, behind the knees, and around the neck. In infants, the
common areas affected are the face, neck, and nappy area. Acute lesions can exude
and show small vesicles. Scratching can cause excoriations and repeated rubbing
causes the skin to thicken (lichenification).
Factors that can aggravate atopic eczema include extremes of temperature, irritants,
stress, infections, and allergens.
Contact dermatitis: Allergic contact dermatitis is a delayed allergic reaction with
an immunologic basis due to substances like nickel in jewellery, chromate in cement,
latex in surgical gloves, perfumes, hair dyes, and certain plants, e.g. poison ivy. The
symptoms rarely develop on first exposure and may only manifest months or years
later following repeated exposure. Irritant contact dermatitis results when a substance
has a toxic effect with no immunologic basis. It occurs on hands after repeated
exposure to irritants like detergents, soaps, or bleach.
Seborrhoeic eczema: This condition is usually confined to areas with a high
secretion of sebum. The likely aetiology is the overgrowth of the yeast Pityrosporum
ovale with a strong cutaneous response that produces the characteristic inflammation
and scaling. It is more common in patients with parkinsonism and HIV disease.
Discoid eczema (nummular eczema): This is a chronic type of eczema seen
commonly in middle-aged males. It is characterised by coin-shaped eczematous
lesions of the extremities.
Venous eczema (stasis eczema, varicose eczema, gravitational eczema): It is
characterized by scaly eczematous plaques confined to the lower legs due to chronic
venous insufficiency seen in varicose veins, peripheral oedema, and non-healing
ulcers.
Asteatotic eczema (winter eczema): It usually affects the lower legs and the backs
of the hands, especially in winter, and appears as dry, cracked skin with a red
eczematous component. It is associated with increasing age and the repeated use of
soaps.
Pharmacological Management
First-line treatment of eczema should include an emollient and a soap substitute for
washing. Topical steroids are used for their anti-inflammatory effects. Systemic
treatments for adult eczema include oral prednisolone, cyclosporine, and azathioprine.
Oral antibiotics are given for secondary bacterial infections.
Emollients: Emollients consisting of fat or oil are used to soften the skin. An
emollient soap substitute for washing is advised.
Topical corticosteroids: These act as anti-inflammatory agents and are useful in
managing eczema. The choice of the topical steroid depends on the site and severity
Dermatology
137
of the skin condition. Some of the corticosteroids used include betamethasone valerate,
clobetasone butyrate, and fluocinolone acetonide. These are available as ointments,
creams, gels, foams, or shampoos for the scalp. Antibiotics and steroid combinations
are used in treating mild bacterial infections of eczematous skin.
Calcineurin inhibitors: These non-steroid immunomodulators inhibit calcineurin
phosphatase, which is important in T-lymphocyte activation. Tacrolimus ointment is
a calcineurin inhibitor used in the treatment of moderate to severe atopic dermatitis
in adults and children over 2 years of age.
Topical imidazoles: Ketoconazole in the form of a shampoo or cream is effective in
the reduction of Pityrosporum ovale on the skin and is useful in the treatment of
seborrhoeic dermatitis.
Systemic Therapy
Oral prednisolone can be used as a short-term treatment in the management of severe
acute eczema.
Cyclosporine is a systemic immunosuppressive agent that blocks activation of
T-lymphocytes and is effective as a short-term bridging therapy in severe chronic
adult eczema. Dose-related nephrotoxicity is a major concern.
Azathioprine can be effective as a monotherapy in adult eczema. Bone marrow
suppression and toxicity are major concerns.
KEY POINTS
• Eczema presents as itchy erythematous scaly patches, especially in front of the elbows and ankles,
behind the knees, and around the neck.
• Irritant contact dermatitis results when a substance has a toxic effect with no immunologic basis.
• Emollients consisting of fat or oil are used to soften the skin.
• Topical steroids are used for their anti-inflammatory effects.
• Systemic treatments for adult eczema include oral prednisolone, cyclosporine, and azathioprine.