📚 Question Bank

Tzanck cells are keratinocytes.

These cells are seen in vesiculobullous disorders, as a result of acantholysis. The keratinocytes lose their polyhedral shapes and characteristically become round with hyperchromatic nuclei and perinuclear halo, as seen in the following image.

Multinucleated giant cells on a Tzanck smear are seen in varicella-zoster and herpes simplex infections.

The image shows punched-out anesthetic lesions characteristic of the borderline spectrum of leprosy. The most unstable form of leprosy is the borderline-borderline type.

This type is rarely seen as it rapidly upgrades towards tuberculoid or downgrades towards lepromatous, based on the immune status of the individual. However, clinical features may lag behind the immunological and histological findings. This leads to numerous skin lesions and with features of both ends of the spectrum.

Lepromatous and tuberculoid types are the most stable. Classification systems of leprosy:

• Ridley Jopling classification:
• Tuberculoid (TT)
• Borderline tubercular (BT)
• Borderline (BB)
• Borderline lepromatous (BL)
• Lepromatous (LL)
• Madrid classification:
• Lepromatous (LL)
• Tuberculoid (TT)
• Borderline/dimorphous
• Indeterminate (early unstable type)
• Indian classification - includes categories under Madrid classification + pure neuritic type
• WHO classification:

Number of skin lesio ns

Nerve involvement Slit skin smear Ridley-Jopling

Paucibacillary Lepros y

up to 5

0-1

Negative on all sites TT, BT

Multibacillary Lepros y

6 or more

2 or more

Positive at any site BB, LL, BL

The most common type of leprosy in India is borderline tuberculoid (BT).

The spectrum of leprosy in India in decreasing order of prevalence:

• Borderline tuberculoid
• Borderline lepromatous
• Lepromatous leprosy
• Pure neuritic type
• Borderline-borderline
• Indeterminate type
• Histoid type

The image shows a hypopigmented skin lesion with pseudopodia and satellite lesions, suggestive of borderline tuberculoid (BT) leprosy.

Features of the lesions of BT leprosy:

• Macules and plaques of various sizes
• Dry, scaly surface
• Pseudopodia or finger-like extensions
• Satellite lesions
• Anesthetic patches
• Anhidrosis over the lesion
• Hair loss

There is asymmetric nerve involvement.

The image shows an ill-defined hypopigmented patch over the face. Normal sensations and a negative slit skin smear suggest indeterminate leprosy.

Indeterminate leprosy is usually the first sign of the disease, found during the screening of contacts of a known case. Clinical features include:

• Hypopigmented or coppery-brown macules, or patches of variable sizes.
• Number of lesions depends on the cell-mediated immunity.
• Sensory loss- rare
• Loss of ability to differentiate temperature

A slit-skin smear is usually negative. It is confirmed by the demonstration of acid-fast bacilli in Fite-stained sections.

Most cases resolve spontaneously. With treatment, the prognosis is good.

The image below shows a high-power Fite-Faraco staining of a skin lesion showing globi of M.leprae.

Option A: Borderline tuberculoid type presents with 1-10 dry, scaly, hypopigmented lesions with or without satellite lesions with diminished sensations and slit skin smear showing scanty bacilli.

Option B: Pityriasis alba presents with single or few hypopigmented macules on the face with normal sensation, normal sweating. There is a history of atopy and waxing and waning of lesions.

Option D- Nevus depigmentosus is a congenital pigmentary disorder that presents with a

non-progressive hypopigmented macule. It usually is present from birth or early childhood and remains stable throughout life.

The earliest sign of leprosy is loss of temperature, usually over the hands and feet.

The onset of leprosy is insidious, with sensory changes often preceding skin lesions by several years. Dysesthesia develops in a progressive manner. The ability to differentiate between hot and cold may be lost before the pinprick sensation. This type of dissociated sensory loss is suspicious for leprosy.

The sensations are lost in the following order:

Temperature gt; Fine Touch gt; Pain gt; Deep touch or pressure Vibration and proprioception are lost in the later stages.

Pure neuritic type leprosy is not included in the Ridley Jopling classification. It is present under the Indian classification.

Classification systems of leprosy:

• Ridley Jopling classification:
• Tuberculoid (TT)
• Borderline tubercular (BT)
• Borderline (BB),
• Borderline lepromatous (BL)
• Lepromatous (LL)
• Madrid classification:
• Lepromatous (LL)
• Tuberculoid (TT)
• Borderline/dimorphous
• Indeterminate (early unstable type)
• Indian classification- includes categories under Madrid classification + pure neuritic type

The ulnar nerve is the most commonly affected nerve in leprosy.

A thickened ulnar nerve may be palpated at the elbow. There can be sensory loss over the palm

(medial) and motor deficit causing a claw hand.

The commonly affected nerves in the order of frequency are:

Ulnar gt; Posterior tibial gt; Median gt; Lateral popliteal gt; Facial

Posterior tibial nerve: Paralysis and contracture of the small muscles of the foot and anesthesia of the sole.

Common peroneal nerve: Difficulty in dorsiflexion and eversion of the foot and anesthesia of the outer border of the foot, causing trauma and plantar ulceration.

The given image shows punched-out lesions, which are characteristic of borderline disease, particularly borderline-borderline and borderline lepromatous.

Polymorphic lesions in borderline-borderline disease produce a geographical or map-like appearance. The two characteristic lesions seen are punched out and inverted saucer lesions.

In the given lesion, two borders are visible. The outer border is ill-defined and the inner border is well-defined. The term punched out refers to the center of the lesions, which look like leprosy has been punched out from that area. It is also called Swiss cheese or annular appearance.

Inverted saucer lesions are raised lesions with ill-defined borders as shown below.

A single skin lesion and histological finding of a granuloma with nerve destruction are suggestive of tuberculoid leprosy.

Borderline types: Granulomas are more prominent in BT than BL types. The nerves may be moderately swollen with infiltrates, but there is no nerve destruction.

Lepromatous leprosy: Granulomas are less and dense uniform macrophage infiltration may be seen. Large numbers of AFBs are also seen, forming clumps.

The given image shows a grenz zone or Band of Unna, which is a band of uninvolved papillary dermis that does not contain granulomas or inflammatory infiltrate. It is absent in tuberculoid leprosy.

The Grenz zone is most prominent in lepromatous leprosy, as there are scarce granulomas to fill up the space. It is also seen in the borderline spectrum.

In tuberculoid leprosy, dermal granulomas, consisting of groups of epithelioid cells with giant cells, are seen. The granulomas are elongated and generally run parallel to the surface, following neurovascular bundles. The granulomas extend up to the epidermis, thereby obscuring the Grenz zone.

The grenz zone is also seen in granuloma faciale and B-cell lymphoma.

The given image depicts lepromatous leprosy. Glove and stocking anesthesia is a late feature. In lepromatous leprosy, the earliest clinical manifestations are dermal.

The early features include:

• Numerous, ill-defined, shiny macules
• Anhidrosis
• Normal sensation
• Nasal symptoms - stuffiness, discharge, epistaxis
• Peripheral oedema due to capillary stasis

Early nerve involvement is asymptomatic. Peripheral nerves are affected first. In the late stages, even facial and corneal nerves can be involved. Loss of sensation begins as patchy and later

becomes extensive. Stocking and glove anesthesia is a late manifestation. The affected skin can become dry and ichthyotic.

The late stage of lepromatous leprosy gives rise to the following features:

• Leonine facies - infiltration of skin folds
• Madarosis - loss of eyelashes eyebrow hair
• Rat-bitten ear - repeated ulceration and healing
• Saddle nose deformity - breakdown of nasal cartilage
• Lepromatous leprosy develops in three stages:
• Early macular stage
• Infiltrated stage - induration due to dermal infiltration, marked in face and ear lobe
• Late nodulo-plaque stage - progress to papules, nodules, and plaques, which ulcerate.

Mononeuritis is the most common form of presentation of pure neuritic form of leprosy.

Pure neuritic form is a variant of leprosy characterized by the isolated involvement of peripheral nerve trunks with the absence of skin lesions. It is more common in India and Nepal.

The clinical features of this variant of leprosy include:

• Nerve thickening
• Sensory neuropathy - pain, tenderness (predominant)
• Loss of function

Nerve trunks of upper limb are more commonly involved. Asymmetric involvement of multiple nerve trunks is also seen. Symmetric polyneuritis is a rare feature. Occasionally, it may present as a nerve abscess.

Nerve biopsy is the gold standard method for diagnosis of pure neuritic leprosy.

The given clinical scenario of a patient with foot drop, skin lesions, and nerve thickening, as shown in the image, is suggestive of leprosy or Hansen’s disease. Neuropathy may continue to progress even after effective MDT. This can lead to secondary impairment for years after completion of therapy.

The superficially located nerves are more commonly involved, especially ulnar, median, radial, peroneal, posterior tibial, greater auricular as well as 5th and 7th cranial nerves.

The given image with shiny papules and nodules on normal skin is suggestive of histoid leprosy. It is characterized by a very high bacillary load.

Histoid leprosy is a rare type of multibacillary leprosy where the bacilli are confined to the lesions and hence, globi are relatively few. The name arises from the microscopic finding

of spindle-shaped histiocytes forming interlacing bands and whorls.

It was initially associated with dapsone monotherapy and irregular treatment, leading to the development of dapsone-resistant bacteria. It is now recognized to arise de novo also.

Lepra reactions are considered to be uncommon in histoid leprosy.

Lepra bonita usually presents with pan-neuritis. It is a diffuse form of lepromatous leprosy and is also called the leprosy of Lucio and Latapi.

Diffuse infiltration of the skin of the face causes obliteration of wrinkles giving a myxedema-like appearance. It appears as a healthy look, leading to the name lepra bonita (beautiful leprosy).

As the disease progresses, the infiltration persists but the skin becomes thinner and atrophic and, consequently, the patient appears to have prematurely aged. Generalized hair loss is also seen.

Lucio phenomenon is a type of lepra reaction seen in these patients and is characterized by well-defined, angular, jagged, purpuric lesions evolving into ulcerations and spreading in ascending fashion and healing with atrophic white scarring, as seen below.

A patient presenting with multiple skin lesions and bacillary index gt; 2+ is classified as multibacillary according to WHO classification. The recommended duration of treatment is 12 months.

Dapsone has good oral absorption and it has a long halflife, averaging 28 hours.

Dapsone or DDS (4,4diamino-diphenyl sulphone) is weakly bactericidal due to the inhibition of dihydropteroate synthase, which inhibits folate synthesis. It is a part of the multidrug therapy for leprosy.

Adverse effects include:

• Mild hemolysis and anemia
• Psychosis.
• DDS syndrome or five-week dermatitis - occurs 5-6 weeks after starting dapsone. It may be fatal.
• It presents with:
• Exfoliative dermatitis
• Hepatosplenomegaly
• Lymphadenopathy
• Fever
• Hepatitis.

Uses of dapsone:

• Steroid sparing drug - long-term therapy for autoimmune blistering diseases
• Adjuvant therapy - bronchial asthma
• CNS-protective - seizure disorders, strokes, glioblastoma

The given scenario of painful lesions in the context of leprosy treatment is suggestive of type 1 lepra reaction, which presents with inflammation of existing skin lesions.

Development of ulcerating lesions following initiation of treatment for leprosy is suggestive of

a severe type 1 lepra reaction. They are commonly seen in the borderline spectrum but are most severe in borderline lepromatous leprosy.

Lepra 1 reactions are due to an enhanced cell-mediated immune response to M.leprae.

They usually present abruptly with redness and inflammation of existing lesions but can cause ulceration in severe cases. It occurs due to a large amount of M. leprae antigens in these patients which results in prolonged and repeated reactions during treatment.

Note: Another form of lepra reaction with ulcerating lesions is the Lucio reaction. It is a rare type of lepra reaction that is seen in patients with lepra bonita. It is often the initial presentation in untreated patients. It is common over extremities and spreads in an ascending fashion. It presents as tender nodules that form jagged ulcers.

The given scenario of painful, erythematous nodules over the limbs in a patient with leprosy is suggestive of erythema nodosum leprosum or type 2 lepra reaction.

It occurs in patients with multibacillary disease - lepromatous and borderline lepromatous leprosy.

The given scenario points to a diagnosis of erythema nodosum leprosum or type 2 lepra reaction. The drug of choice is oral corticosteroids.

Clofazimine is indicated in chronic ENL, which is steroid-refractory or when steroids are contraindicated.

Thalidomide is superior to steroids in controlling ENL and can be used for severe ENL in young men. However, it is generally avoided in women due to its devastating teratogenic side effects. It may be considered in severe ENL but must be used cautiously, with double contraception measures. It also causes peripheral neuropathy and, hence, would be avoided in this patient with lepromatous neuropathy. The high cost and restricted availability also limit the use of this drug.

Rifampicin should be avoided as it is highly bactericidal. The massive release of bacterial antigens may aggravate the lepra reaction.

The given scenario of painful nodules in a woman with leprosy is suggestive of erythema nodosum leprosum (ENL). The likely drug used in this immunosuppressed young woman is clofazimine, which causes deposition of crystals in the intestinal mucosa, liver, lymph nodes, and spleen, not renal tubules.

Clofazimine is a brick red, fatsoluble crystalline dye with a weak bactericidal action against M. leprae through an unknown mechanism. It also has an antiinflammatory effect, which is useful in the management of ENL reactions.

The most noticeable side effect is skin discoloration, ranging from red to purple-black, the degree of discoloration depends on the dose and amount of leprous infiltration. It generally fades within 6–12 months after stopping clofazimine, however, traces of discoloration may remain even for up to 4 years. Urine, sputum, and sweat may turn pink.

It also produces scaling and ichthyosis of the shin and forearms.

Crystal deposition in the wall of the small bowel occurs as the drug is excreted into the bile. This causes GI side effects that range from mild cramps to diarrhea and weight loss.

Note: Corticosteroids are the first-line drugs in the treatment of ENL but would be avoided in this immunosuppressed patient.

The given images showing a hypopigmented lesion along with tibial nerve thickening are is suggestive of leprosy. Lepromin test is a prognostic test used in the classification of Leprosy. It has no diagnostic purpose.

It involves performing an intradermal injection of the lepromin antigen (synthesized from M. leprae) on the flexor surface of the forearm. It is a skin test for delayed hypersensitivity, is the only method for studying immunity in leprosy.

• Positive test - good cell-mediated immunity and points towards the tuberculoid side of the spectrum
• Negative test - poor cell-mediated immunity and POINTS towards the lepromatous side of the spectrum.

The antigens used in lepromin test are:

• Lepromin A (from armadillo-derived lepra bacilli)
• Dharmendra antigen

First is the early reaction of Fernandez, which consists of erythema and induration developing in 24-48 hours and usually remaining for 3-5 days; it is usually poorly defined and carries less significance.

The second and more meaningful result is the late reaction of Mitsuda, starting at 1-2 weeks (7-10 days), reaching a peak in three or four weeks, and gradually subsiding over the next few weeks. At end of 21 days, if there is a nodule gt;5mm in diameter, the reaction is said to be positive.

The test is used for the following purposes:

• To classify the lesions of leprosy patients.
• To assess the prognosis and response to treatment.
• To assess the resistance of individuals to leprosy.
• To verify the identity of candidate lepra bacilli.

Option A: Sensory testing is useful to detect hypoesthesia and nerve involvement of leprosy. Option B: Slit skin smear shows the presence of acid-fast bacilli.

Option D: Biopsy would reveal few tuberculoid granulomas and plenty of foam cells, which are diagnostic of leprosy.