Controversial MCQ: Steroids Vs Thalidomide for ENL

MCQ

There is confusion on these choices :--

Best treatment for Type 2 lepra reaction is (WBPG 2011)

          1) Steroids      2) Thalidomide 3) Dapsone

          4) Clofazimine

Unfortunately, this question has inadequate information. So often, this question will have different answers by different faculty specialists. But I will try to analyze this question.

After extensive literature search, no double blinded studies were found of a direct comparison between steroids and Thalidomide for Type 2 lepra reaction (ENL)

All studies have been on use of thalidomide as an add-on combination agent when patients develop recurring ENL while tapering steroids for it. The various views and guidelines for ENLs by established agencies are as under:

·     FDA: Thalidomide was approved by the FDA in the USA in 1998 ‘’in the treatment of the cutaneous manifestations of moderate to severe ENL and as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrences’’. It also states that thalidomide is effective in steroid dependent patients and allows steroid withdrawal.

      (Ref: http://www.fda.gov/ohrms/dockets/dockets/05p0167/05p-0167-cp00001-Tab-05-Thalidomide-Brochure-vol1.pdf)

·      WHO Expert Committee: Corticosteroids are the mainstay in treatment of ENL. WHO has issued conflicting statements with respect to the use of thalidomide. They range from “WHO does not support the use of thalidomide in ENL” (www.who.int/lep/research/Reactions.pdf. Management of reactions in leprosy) to “there is no role for thalidomide in the management of leprosy”(http://www.ops-oms.org/English/AD/DPC/CD/thalidomide.htm) 

 

·     The ILEP Technical Bulletin: Thalidomide is a very effective drug for ENL but its use is limited by the potential teratogenicity.

     (Ref: http://www.ilep.org.uk/fileadmin/uploads/Country_Pages/Sri_Lanka/Guidelines_Management_Lep_Reactions.pdf)

·     Indian studies:

       1) Thalidomide works faster than steroids . It controls ENL in 48-72 hrs in most cases.

       (Ref: Chaudhry NS, et al. Our experience of the use of thalidomide in the steroid-dependent severe erythema nodosum leprosum. Indian J Dermatol Venereol Leprol 2009;75:189-90)

       2) Poor control with corticosteroids in patients with chronic ENL 

        (Ref: Pocaterra L, Jain S, Reddy R et al. Clinical course of erythema nodosum leprosum: an 11-year cohort study in Hyderabad, India. Am J Trop Med Hyg. 2006 May; 74(5):868-79)

Thus, in finality the indications of thalidomide are

   1) Men or post-menopausal women with difficult to manage ENL

   2) Recurrent ENL not responding to steroid

   3) Steroid dependent cases who relapse on steroid withdrawal, allowing for steroid withdrawal

   4) Steroid sparing in patient's of ENL with diabetes, TB or hypertension

Chart for treatment schedule for ENL (Ref: Walker SL, et al. Lepr Rev 2007)

In this MCQ then, the answer would be- 

DOC- steroids (first line therapy)

Thalidomide (2nd line therapy)

Best drug (in the Indian Set-up) - Steroids

Pathergy test

**Pathergy phenomenon is defined as a state of altered tissue reactivity that occurs in response to minor trauma like a needle prick (with a blunt needle)

**Pathogenesis of pathergy phenomenon
Although the exact mechanisms underlying pathergy phenomenon are unknown, skin injury caused by needle prick apparently triggers a cutaneous inflammatory response and creates a papule/pustule. This suggests an increased or aberrant release of cytokines from keratinocytes or other cells in the epidermis or dermis. The specificity of skin pathergy reaction is very high especially in Behcets disease (about 99%), especially when it is positive at 48 h

**Types of pathergy tests

1) Oral Pathergy test: Pricking the oral mucosa with a needle and looking at ulcer creation

Oral Pathergy test- Pricking with a 20- gauze needle.

Positive test: Ulcer formation at 48 hrs

2) Skin Pathergy test:  2 needle pricks with 20 gauge needle are given on the flexor aspect of the forearms at an angle of 30 degree till 1.5 mm depth. Readings are taken after 48 hrs of the needle prick. A 1-2mm papule that is usually felt by palpation and which is surrounded by an erythematous halo is formed on the skin. The papule may remain as a papule or transform into a pustule. The pustule becomes prominent in 24 h, becomes maximum in size in 48 h, and disappears in 45 days. Erythema without induration is interpreted as a negative result. Histopathology of the new lesion demonstrates inflammation with mononuclear cells.

**Seen in
1) Behcet's disease- Positive pathergy reaction is very important for the diagnosis of Behcet's disease in patients with only recurrent oral ulceration plus one of the other criteria (recurrent genital ulceration, eye lesions, skin lesions). The test has also been used as an indicator of disease activity in patients with Behcet's disease. It is one of the 4 minor criteria in its diagnosis
2) Pyoderma gangrenosum
3) Rheumatoid arthritis
4) Inflammatory bowel disease
5) Eosinophilic pustular folliculitis
6) Healthy individuals
7) Sweets syndrome- rare but described

Ref: Sequeira FF, Daryani D. The oral and skin pathergy test. Indian J Dermatol Venereol Leprol 2011;77:526-30

MCQs

1) Pathergy test is most characteristic of
a. Behcets disease
b. Dermatitis herpetiformis
c. Sweet syndrome
d. Pyoderma gangrenosum
Answer: a

2) A patient presents with recurrent painful oro-genital ulcers. The test which will help in leading to a diagnosis is
a. Oral biopsy
b. Genital biopsy
c. Pathergy test
d. Eye examination

Answer: c
Expl: Positive pathergy reaction is very important for the diagnosis of Behcet's disease in patients with only recurrent oral ulceration plus one of the other criteria (recurrent genital ulceration, eye lesions, skin lesions)

3) What is false about pathergy test (PGI type)

a. Screening test for Behcets disease
b. Indicator of disease activity in Behcet's disease
c. Double prick is better than a single prick
d. Independent risk factor for occurrence of postoperative complications in Behcet's disease.
e. Sharp needle increases the positivity rate

Answer: a. e

Expl: The low sensitivity of pathergy test prevents it from being used as a screening test. Use of a blunt (reusable, sterilized) needle increases the frequency and intensity of a positive skin pathergy test as it is more traumatic.  

Psoriasis- Click the book

Psoriasis

 Classical well defined erythematous plaque of psoriasis with silvery scales

In Brief

1. Psoriasis is a chronic, immune-mediated disorder . Etiology is polygenic. There has to be a genetic predisposition combined with environmental triggers, e.g. trauma, infections or medications
2. The underlying pathophysiology involves T cells and their interactions with dendritic cells and cells involved in innate immunity, including keratinocytes
3. Sharply demarcated, scaly, erythematous plaques characterize the most common form of psoriasis, which is also called as psoriasis vulgaris (vulgaris = common). Psoriatic arthritis is the major associated systemic manifestation. Recently, numerous metabolic derangements have been seen in psoriasis (more about this below), prompting calls for it to be thought of now a metabolic disease rather than only a pure cutaneous and joint disease.

Introduction  

1. The prevalence of psoriasis is said to be 2% of the world’s population.
2. Genetically, psoriasis is associated mostly with HLA-Cw6 (some clinicians have designated patients with early-onset psoriasis, a positive family history of psoriasis, and expression of HLA-Cw6 as having type I psoriasis and those with late-onset disease, no family history, and a lack of expression of HLA-Cw6 as having type II psoriasis) . HLA-B27 allele is a marker for sacroiliitis-associated psoriasis and reactive arthritis. By far the most important genetic region is PSORS1 (on chromosome 6p), which is estimated to account for up to 50% of psoriasis risk. 

Pathogenesis

1. Primarily it is a T cell mediated disease
2. Dendritic cells are also known to be involved (thought to release IL- 23)
3. Although activated neutrophils could contribute to its pathogenesis, they are not considered to be the primary cause of psoriasis ( However, the presence of neutrophils in the epidermis, either in spongiform pustules of Kogoj or in microabscesses of Munro, is a typical histopathologic feature of psoriasis, especially acute or pustular forms)
4. Prominent angiogenesis is observed in plaques of psoriasis (This is responsible for the Auspitz sign which will be described in detail below)
5. Increased amounts of Th1 cytokines (IFN-γ and IL-2) are observed, whereas levels of the anti-inflammatory cytokine IL-10 are reduced. 
6. IL-12, IL-23 and IL-15 are likely to contribute to the disease. IL-23 plays a key role in the Th17 mediated inflammatory pathway while IL-12 is a key cytokine in the Th1 inflammatory pathway. Ustekinumab is a newer humanized monoclonal antibody, which selectively binds to IL-12 and IL-23. So ustekinumab can potentially inhibit both inflammatory pathways. (ustekinumab was asked recently in an entrance exam)

 Triggering Factors

1.  Infections- Streptococus (typically triggers gutatte psoriasis) and HIV. Provoking infections have been observed in up to 45% of psoriatic patients. Streptococcal infections, especially pharyngitis, are the most common offenders (This was asked recently in DNB) 
2. Sudden withdrawal of systemic steroids (Hence, systemic steroids are generally not given in psoriasis- This question has been asked)
3. Hypocalcemia (specially for pustular psoriasis)
4. Trauma-- Seen clinically as Koebner's phenomenon
5. Drugs- B-Blockers, NSAIDS, Chloroquine and Lithium
6. Alcohol, Smoking
7. Obesity
8. Emotional stress
9. Sunlight- Some patients worsen, some improve 

Types Of Psoriasis:

1) Psoriasis vulgaris (Chronic Plaque Psoriasis) - Typically presents as sharply demarcated, erythematous plaques on extensor aspects like elbows, knees, knuckles, lower back. The lesions typically have a triad of erythema (due to new blood vessel synthesis, thickening (due to thickened epidermis) and scale (due to faulty epidermal keratinisation and faulty exfoliation)   
 

Above/Below: Erythematous scaly plaque on the extensor Knee

 

 2) Gutatte psoriasis- Typically in children and young adults. Generally a fall-out of an  underlying streptococcal infection (pharyngitis- Was asked in DNB)

3)  Erythrodermic psoriasis- Severe form. Generalized erythema and scaling affecting > 80% of the body surface. 

4) Flexural (Inverse psoriasis)- Flexural psoriasis also called as inverse psoriasis is typically non scaly and only shiny erythema is seen. Seen in the flexural sites like inframammary area, groins, axillae, etc. 

 












 

Above: Flexural Psoriasis over the abdominal fold in a obese patient with pendulous abdomen.  Note that there is no scaling  (question for PGI exam)

5) Nail psoriasis-  Nail involvement has been reported in 10–80% of psoriatic patients. The fingernails are more often affected than the toenails. Patients with nail involvement appear to have an increased incidence of psoriatic arthritis.

Features of nail psoriasis

  
1) Oil drop or salmon patch of the nail bed- This lesion is a translucent, yellow-red discoloration in the nail bed resembling a drop of oil beneath the nail plate. This patch is the most diagnostic sign of nail psoriasis (Important question for exam)
2) Pitting of the proximal nail matrix- Pitting is a result of the loss of parakeratotic cells from the surface of the nail plate- question for exam. Pitting is due to affection of the proximal matrix - question
3) Beau's lines- These lines are transverse lines in the nails due to intermittent inflammation causing growth arrest lines
4) Leukonychia (white streaks on nail)
5) Subungual hyperkeratosis- Excessive proliferation of the nail bed
6) Onycholysis - Onycholysis is a white area of the nail plate due to separation of the nail plate from its underlying attachment to the nail bed (secondary to subungual hyperkeratosis)  - question for exam
7) Nail plate crumbling
8) Splinter hemorrhage/dilated tortuous capillaries in the dermal papillae- Splinter hemorrhages are longitudinal black lines due to minute foci of capillary hemorrhage between the nail bed and the nail plate. This is analogous to the Auspitz sign of cutaneous psoriasis, which is the pinpoint bleeding seen beneath the psoriatic plaques
9) Red lunula

Above: Nail pitting in psoriasis (superficial, Irregular)

 Above: Red patch on nail (called as Salmon patch/ Oil drop sign) - Imp.question for exam

Above: Subungual hyperkeratosis, Also you can see Onycholysis (Separation of nail plate from nail bed)

 
6) Psoriatic Arthritis (PsA)- Psoriatic arthritis occurs in 5–30% of patients with cutaneous   psoriasis. Psoriatic arthritis is more prevalent among patients with relatively severe psoriasis. Most commonly skin lesions precede joint involvement

         Risk factors for PsA  (Ref: Bolognia,3rd Edn)

• Early age
• Female gender
• Nail Involvement-question
• Polyarticular involvement
• Genetic predisposition
• Radiographic signs of the disease early on

 Types of PSA
1. Mono- and asymmetric oligoarthritis- Inflammation of the interphalangeal joints – both distal (DIP) and proximal (PIP) – of the hands and feet is the most common presentation of psoriatic arthritis- common question for exam. Involvement of the PIP or both the DIP and PIP joints of a single digit can result in the classic “sausage” digit. In contrast to rheumatoid arthritis, the metacarpophalangeal (MCP) joint is an unusual site for psoriatic arthritis. 
2. Only DIP involvement- Classical form (though very uncommon to see in practise)- common question for exam
3. Rheumatoid arthritis-like presentation
4. Arthritis mutilans
5. Spondylitis and sacroiliitis- Mainly with HLA-B27-positive status 

Treatment of PsA
Methotrexate  has long been the mainstay drug for starting therapy in PsA- common question for exam.Other drugs are NSAIDS, Leflunamide, sulphasalazine and cyclosporine. As a general consensus, biologic agents are reserved for resistant disease. However, they may be considered as first line for the treatment of enthesitis/dactylitis and those with predominantly axial disease. Most widely used and studied are those which block TNF-α, a potent pro-inflammatory cytokine. These include etarnercept, infliximab and adalimumab all of which have received FDA approval for treatment of PsA. 


7) Pustular Psoriasis- Most severe form (This fact was asked recently in DNB). Divided into generalized pustular psoriasis and localised pustular psoriasis. 

Selected types
Generalised	Von-Zumbusch type
	Annular type
	Of pregnancy (Impetigo herpetiformis)
Localised type	Of palms and soles (Palmoplantar psoriasis)
	Of nails (Acrodermatitis continua)

• Generalised form= Von Zumbusch type is a generalized eruption starting abruptly with erythema and pustulation. The skin is painful during this phase, and the patient has a fever and feels ill. After several days, the pustules usually resolve and extensive scaling is observed. Look for words "LAKES OF PUS" OR "SHEET OF PUS" in questions on Von-Zumbush psoriasis (Very commonly asked with these pointer words)

 (Ref: emedicine)

 Localised form (sole)

(Ref: emedicine) 

 

8. Palmoplantar Psoriasis

  Below: Palmar Psoriasis

  
  Below:Plantar Psoriasis

9. Sebopsoriasis-  In seborrhoeic areas like scalp, face, retro-auricular area, central chest and upper back (Was asked in PGI). The scales sometimes have an asbestos-like appearance and can be attached for some distance to the scalp hairs (pityriasis amiantacea- Question)

Histopathology




 (Ref: www.vitajointrelief.com)

1) Regular elongation of rete ridges 
    (rete ridges are narrow towards the surface and broad at the base- See below)

 Ref: dermnet.com

2) Acanthosis- Thickening of stratum spinosum

3) Parakeratosis (Nuclei in stratum corneum- Common Question)

 

 4) loss of the granular cell layer 
5) Formation of spongiform pustules of Kogoj (Neutrophils accumulating in stratum spinosum)- Common Question
6) Munroe's microabscesses - Common Question
(Neutrophils accumulating in stratum corneum)
7) Capillary vessels within the superficial dermis are dilated

 Associations between Psoriasis and Other Diseases

 1. Cardiovascular diseases, e.g. myocardial infarctions, pulmonary emboli, peripheral arterial disease and cerebrovascular accidents are more common. This is largely due to an increased risk of obesity, hypertension and diabetes mellitus (components of the metabolic syndrome)- question for exam
2. Non-alcoholic steatohepatitis (NASH)- characterized by fatty infiltration, periportal inflammation and focal necrosis of liver.
3. Crohn’s disease, ulcerative colitis and psoriasis share an association with sacroiliitis and HLA-B27 positivity

Lasers in psoriasis
The excimer laser which is a hand held device—approved by the Food and Drug Administration (FDA) for treating chronic, localized psoriasis plaques—emits a high-intensity beam of ultraviolet light B (UVB) of a very specific wavelength -- 308 nanometers to a localized area of psoriatic skin (not to the whole body), thus  selectively targets affected skin and prevents irradiation of surrounding healthy skin. Like the excimer laser, the pulsed dye laser (PDL) is approved for treating chronic, localized plaques. PDL destroys the tiny blood vessels that contribute to the formation of psoriasis lesions

Prognosis
Although the course of this disease is chronic, periods of complete remission do occur in about 15% of patients. 

Scoring in psoriasis
1. PASI (Psoriasis Area Severity Score)- Erythema, Thickness and scaling is numbered (between 0-4) for 4 anatomic body areas(Head, Trunk, upper limb, Lower limb). Maximum score possible=72
2. NAPSI - Score for nail involvement (Nail Psoriasis Severity Index)

Signs in psoriasis- common question for exam
1) If the superficial silvery white scales are removed via scratching (grattage method), a characteristic coherence is observed, as if one has scratched on a wax candle (“signe de la tache de bougie”). Subsequently, a surface membrane (Bulkeley membrane) is seen, which will also come off as a whole. If this membrane is removed, then a wet surface is seen with characteristic pinpoint bleeding. This finding, called Auspitz sign, is the clinical reflection of elongated vessels in the dermal papillae together with thinning of the suprapapillary epidermis.

Auspitz sign is attributed to parakeratosis, suprapapillary thinning, elongation of dermal papillae and dilatation and tortuosity of the papillary capillaries.

However, Auspitz sign is not sensitive or specific for psoriasis. Not sensitive, because in one study, out of 234 patients it was seen in 41 patients of psoriasis. Also it is not seen in inverse psoriasis; pustular, erythrodermic psoriasis; guttate psoriasis. Not specific because it is also seen in nonpsoriatic scaling disorders, including Darier's disease and actinic keratosis.

Stages of auspitz sign
1) remove scales
2) remove a thin membrane called bulkeley membrane
3) pin point bleeds

2) Woronoff’s ring is a ring of hypopigmentation around a psoriatic plaque- question

MCQs

1) What is false about psoriasis?
A) can involve head, face and ears
B) 5% have arthritis
C) Abscess can be seen
D) Red scaly lesions in inframammary region

Answer: D

Expl: See above

2) Psoriasis is characterised by all except
A. Definite pink plaque with clear margin
B. In children disappear in 2 wks to reappear again
C. Always associated with nail infection
D. Involves knee and elbow

Answer: C

Expl: See above

3) Treatment of psoriasis include all except
A. Retinoids
B. Mtx
C. Cyclosporin
D. Oral corticosteroids

Answer: D

Expl:See above

4) The only definite indication for giving systemic corticosteroids in psoriasis is:
A. Psoriatic erythroderma with pregnancy
B. Psoriasis in a patient with alcoholic cirrhosis
C. Moderate arthritis
D. Extensive lesions

Answer: A

Expl: See above 

5) All are misnomers, except
A) Impetigo herpetiformis
B) Pyoderma gangrenosum
C) Butcher’s Wart
D) Herpes gestationis
 

Answer is C
Expl: A) Impetigo herpetiformis= pustular psoriasis in pregnancy
B)  Pyoderma gangrenosum= not pyoderma, not gangrene. it is a  neutrophilic dermatosis presenting as very painful leg ulcers
C) Butcher's wart are actual warts
D) Herpes gestationis is not herpes in gestation (it is the other name for pemphigoid gestationis)

6) Nail changes in psoriasis are all except
A)Subungual hyperkeratosis
B) Onycholysis
C) Splinter haemorrhages
D) Thinning of nail plate 

Answer is D (thinning is typical of lichen planus) 

7) Coal tar and ultraviolet radiation are traditionally given in
A) Ingram regimen
B) Welsh regimen
C) Kligman regimen
D) Goeckermans regimen

Answer is D

• Goeckerman therapy- See above
• Ingram- See above
• Welsh- amikacin along with cotrimoxazole for actinomycotic mycetoma. In Modified Welsh regimen, in addition to amikacin and cotrimoxazole, there is rifampicin.
• Kligman- For melasma (triple combination of topical steroids+ Topical hydroquinone+ Topical tretinoin)- DNB question

8)  Scoring system in nail psoriasis is

A) PASI
B) SCORAD
C) NAPSI
D) SCORTEN
 

Answer is NAPSI
Expl: PASI= Psoriasis Area Severity Score

SCORAD= Score (SCOR) for Atopic dermatitis (AD)

NAPSI = Nail (NA) Psoriasis Severity Index (PSI)

SCORTEN= Score (SCOR) for Toxic Epidermal Necrolysis (TEN)

 9) Phototherapy is useful for all except

A) Psoriasis 

B) Uremic pruritus

C) Atopic dermatitis

D) Actinic keratosis

Answer is D

Actinic keratosis is a premalignant skin disease subsequent to sun induced chronic damage

10) The lasers which has been employed in psoriasis is

a) Long pulse Nd:YAG
b) Q-switched Nd:YAG
c) Excimer
d) Fractional laser

Answer is excimer
Expl: See above 
        Long pulse Nd:YAG is for hair removal and vascular anomalies (eg: Hemangiomas and port wine stains)
        Q-switched Nd:YAG is for hyperpigmentation (Tattoo and pigmented birth marks)
        Fractional lasers are for post acne scars and other skin surface irregularities.

11) Psoriatic arthritis has all feature except (PGI type)

A) Enthesitis
B) HLA-B27 is strongly supportive of peripheral disease
C) Nail involvement predicts development of psoriatic arthritis
D) Asymmetric, oligoarticular arthritis is the commonest presentation
E) High BMI patients have higher risk

Answer: B
Expl: See above