📚 Question Bank

The clinical scenario describes unilateral seizure activity with a port-wine stain, suggestive of Sturge–Weber syndrome (SWS), a severe neurocutaneous disorder.

The port-wine stain is a vascular plaque (capillary malformation) over the lateral aspect of the forehead mainly involving the territory of ophthalmic(V1) and maxillary (V2) division of the trigeminal nerve. It presents with ipsilateral leptomeningeal angiomas and contralateral seizures or hemiparesis.

Muir–Torre syndrome is a rare autosomal dominant disorder of DNA mismatch repair.

It occurs due to mutation in one of the DNA mismatch repair genes (MSH2, MLH1, MSH6). It is characterized by sebaceous gland neoplasms, keratoacanthomas associated with gastrointestinal and genitourinary malignancies.

The CT brain shows tram-track cortical calcifications, a characteristic feature of Sturge-Weber syndrome.

It occurs due to leptomeningeal hemangioma, resulting in a vascular steal affecting the subjacent cortex and white matter producing localized ischemia and calcification.

The image shows a periungual fibroma or Koenen tumor, which is characteristic of tuberous sclerosis (TS). They appear at or after puberty as smooth, firm, flesh-colored excrescences emerging from the nail folds.

Other cutaneous features of tuberous sclerosis:

• Angiofibromas - Firm, discrete, red-brown, telangiectatic papules, 1 to 10 mm in diameter that become more extensive at puberty and then remain unchanged. They extend from the nasolabial furrows to the cheeks and chin and are occasionally found in the ears.
• Shagreen patch - An irregularly thickened, slightly elevated, soft, skin-colored plaque, usually
• in the lumbosacral region.
• Ash-leaf macule - White ovoid or ashleafshaped macules, 1–3 cm in length, most easily detectable by examination under Wood’s light, are frequently present on the trunk or limbs. They are a valuable physical sign as they may be found at birth or in early infancy, some years before other signs of the disease develop.
• Other cutaneous manifestations- include firm fibromatous plaques, especially on the forehead and scalp, soft pedunculated fibromas around the neck and axillae, and poliosis.

Buttonhole sign is seen in type 1 neurofibromatosis (Von Recklinghausen's disease).

Neurofibromas can be invaginated into the subcutis with the tip of the index finger back and they reappear after the pressure is released. This is the buttonhole sign.

This sign is also positive in anetoderma and dermatofibroma. The image below shows a dermatofibroma.

The image shows fish-like scales with dry skin, characteristically seen in ichthyosis vulgaris (icthyos-fish).

Ichthyosis vulgaris is an autosomal dominant disorder, that occurs due to reduced or absence of filaggrin protein and granular layer. It occurs when the skin does not shed the dead skin cells.

This leads to dry, dead skin cells that accumulate in small patches on the surface, especially on the arms and legs. It’s also called the 'fish scale disease'.

Features Defect Scales

Spared are as

Associatio ns

Ichthyosis Vulgaris Filaggrin protein Fine scales

Flexors and face

Keratosis pilarisHyperlinear palms

XLR-Ichthyosis

Steroid sulphatase enzyme

Dark plate-like adherent scal es

Palms and soles

Corneal opacitiesCryptorchid ism

X-linked recessive ichthyosis is a disease affecting only males and presenting with large, generalized dirty brown-black scales encroaching flexures along with cryptorchidism.

It is due to a mutation in the STS gene encoding steroid sulfatase.

At the age of 2–6 months, usually large thick dark brown to yellowbrown hyperkeratosis develop covering the trunk, the extremities and the neck. Skin biopsy shows hyperkeratosis with hypergranulosis. Palms, soles, and larger flexures are spared. Deep stromal corneal opacity is a frequent finding.

The clinical picture shows a neonate encased in a shiny, parchment-like membrane (collodion baby) suggestive of a disorder belonging to the autosomal recessive congenital ichthyosis spectrum.

Ichthyosis vulgaris is not a part of this disease spectrum. It does not present at birth and is therefore an unlikely diagnosis.

Ichthyosis vulgaris is an autosomal dominant condition caused due to a mutation in the filaggrin gene (FLG). It develops in the first few months of life. Patients exhibit accentuated palmar and plantar creases and have dry scaly skin. The scales appear light grey and cover the extensor surfaces of the limbs and the trunk. It usually spares the groin and larger

flexures. Immunohistochemistry reveals an absent or markedly reduced filaggrin signal. Autosomal recessive congenital ichthyosis spectrum includes the following:

• Harlequin ichthyosis (HI)
• Bathing suit ichthyosis (BSI)
• Lamellar ichthyosis (LI)
• Congenital ichthyosiform erythroderma (CIE)
• Self- improving congenital ichthyosis (SICI)
• Transient manifestations, such as collodion baby.

A neonate encased in a shiny parchmentlike membrane is called a collodion baby. It is the presentation for all autosomal recessive congenital ichthyoses (except for Harlequin ichthyosis).

The membrane usually peels off within the first 4 weeks of life. Initially, the clinical presentation can be quite severe and often includes ectropion and everted lips of different degrees. This later clears.

Collodion babies look alike at birth, but later take different clinical courses such as:

• Lamellar ichthyosis - shedding of the collodion membrane is followed by development of large dark grey/brownish scales affecting the trunk and scalp, but sparing the face and extremities
• Bathing suit ichthyosis - develop a lamellar type of ichthyosis that spares the face and the extremities and follows a bathing suits distribution
• Congenital ichthyosiform erythroderma
• Selfhealing collodion baby
• Acral selfhealing collodion baby

Note: That several syndromic types of congenital ichthyosis such as trichothiodystrophy or Gaucher syndrome type 2 also typically present as collodion baby.

The image shows Lisch’s nodules, the most common ocular manifestation of neurofibromatosis type 1.

These are melanocytic hamartomas, which are usually brown or yellow in color. They are found as round elevations on the surface of the iris, often visible to the naked eye. However, optimal evaluation is done by slit-lamp examination.

They do not produce visual impairment.

The images show widespread neurofibromas and optic nerve glioma which are diagnostic of neurofibromatosis-I (NF-I). Confetti skin lesions are not seen in NF, but in tuberous sclerosis.

It is an autosomal dominant disorder.

For diagnosis of NF-I, two or more of the following should be present:

• 6 or more café-au-lait spots
• 2 or more neurofibromas or one plexiform neuroma
• Freckling in the axillary or inguinal region
• 2 or more Lisch nodules
• Dysplasia of the sphenoidal or tibial bones
• First degree relative with NF1
• Optic gliomas

The image below shows multiple café-au-lait spots distributed over the body.

The image below shows neurofibromatosis: axillary freckling and café-au-lait spots.

The given image shows multiple telangiectasias of conjunctival vessels. This along with DNA repair defect point towards ataxia-telangiectasia (AT) or Louis–Bar syndrome. Progressive cerebellar degeneration is the first clinical manifestation in ataxia-telangiectasia, presenting at about 1 year of age.

AT is a rare autosomal-recessive disorder. There is chromosomal instability due to inactivating mutations in the ATM gene. The ATM protein kinase plays a key role in the control of

double-strand break DNA repair.

It is a multisystem disorder characterized by ataxia and mucocutaneous telangiectasia. Cutaneous features include:

• Telangiectasias - initially conjunctival, most prominent on face
• Premature hair greying
• Caféaulait spots
• Pigmentary changes - poikiloderma.
• Other cardinal features of AT are:
• Immunodeficiency - increased susceptibility to infections
• Hypogonadism
• Sensitivity to ionizing radiation
• Insulin resistance
• Predisposition to cancer

Port-wine stain represents progressive ectasia of superficial vascular plexus mostly involving the face. It does not resolve spontaneously and is usually treated by a 585 nm pulsed dye laser.

The image shows phrynoderma. It is not associated with vitamin D deficiency.

Phrynoderma (toad skin) is common in children in the 5-15 year age group. Earlier thought to be purely due to vitamin A deficiency, phrynoderma has now been associated with other nutritional deficiencies, including those of B complex, riboflavin, vitamin C, vitamin E, and essential fatty acids and malnutrition.

It is a non-specific finding that can be associated with various conditions:

• Liver cirrhosis
• Malabsorption syndromes
• Anorexia nervosa
• Alcohol abuse
• Nutritional deficiency following bariatric surgery

It manifests as groups of papules, each one around 3-4 mm in diameter, with a central keratotic plug. The papules have a follicular distribution and give the skin a rough texture. The elbows and knees are the most commonly affected areas, but the buttocks and extensor surfaces of the limbs may also be affected.

All patients with phrynoderma should have their vitamin A levels measured.

Treatment involves the correction of poor diet and administration of multivitamin preparations.

The given image shows peripheral edema and a ‘flaky paint’ dermatitis seen characteristically in kwashiorkor.

This dermatosis has been likened to ‘cracked skin’, ‘peeling paint’, ‘enamel paint’, ‘flaky paint’ or ‘crazy paving’ due to the typical scales and irregular fissuring noted on examination. Over time, more defined plaques may arise that may be more concentrated in areas of friction such as the intertriginous areas.

Peripheral edema is a consistent feature due to the associated hypoproteinaemia. Abdominal distention is a feature observed in children and has been attributed to hepatomegaly from increased fatty deposition due to a lack of available apolipoproteins.

Option A: Loss of subcutaneous tissue, growth stunting, dyspigmentation, and desquamative changes is seen in marasmus.

Option B: Casal's paint necklace is a lesion seen around the neck, which is a characteristic feature seen in pellagra, which is caused due to the deficiency of niacin or nicotinic acid.

Option C: Phrynoderma or toad skin is seen in vitamin A deficiency. It is seen in deficiency of vitamin B complex, C, E, and essential fatty acids as well.

The image shows acrodermatitis enteropathica. It is classically associated with:

• Diarrhea
• Alopecia
• Periorificial and acral cutaneous eruptions.

Zinc deficiency can be inherited (acrodermatitis enteropathica) or acquired.

Acrodermatitis enteropathica is an autosomal recessive disorder caused by a mutation in the intestinal zinc transporter gene, SLC39A4, which leads to deficiency of zinc.

Children commonly present with symmetrical, eczematous plaques that become vesicular, bullous, pustular or erosive with characteristic crusting at the edges. The perioral eruption usually spares the upper lip, giving it a ‘Ushaped’ or ‘horseshoeshaped’ appearance.

Zinc supplementation rapidly improves the condition within 24 to 48 hours. If untreated, it maybe fatal.

Mnemonic: DEAL for acrodermatitis enteropathica:

• Diarrhoea
• Eczematous dermatitis
• Alopecia
• Lethargy

The neonate is most likely suffering from Harlequin ichthyosis, as evidenced by the presence of armor-like skin.

It is the most devastating type of autosomal recessive congenital icthyosis. It is due to mutations of the ABCA12 gene. The gene plays a role in lamellar body formation in the stratum granulosum and desquamation of the stratum corneum.

It presents in the neonatal period with armorlike skin (truncal plates with fissuring). It can impair body movement and breathing. Bilateral ectropion and eclabium are present. Respiratory problems are the major cause of death due to alveolar collapse in neonates. They are also prone to skin and lung infections.

Defective lamellar bodies in the stratum granulosum seen in electron microscopy are pathognomic of Harlequin ichthyosis. In early life, constant supportive care is required. Treatment includes moisturizing cream, antibiotics, etretinate, or retinoids.

Other options -

Option A) Ichthyosis vulgaris - The most common type of ichthyosis, involving mutations in filaggrin protein. Filaggrin is an epidermal protein that helps retain moisture in the stratum corneum. Ichthyosis is not present at birth but develops during the first months of life. The scaling usually involves the extensor surfaces of the extremities with flexural sparing. They are strongly correlated with atopic dermatitis and other forms of atopy such as allergic rhinitis, asthma, etc.

Option B) Bathing suit ichthyosis is a type of congenital ichthyosis caused by mutations in the TGM1 gene. It presents as a collodion baby at birth where the neonate is encased in a shiny parchmentlike membrane. Shedding of the collodion membrane is followed by the development of large dark grey/brownish scales affecting the trunk and the scalp, but sparing the face and extremities resembling a bathing suit. The disease tends to become worse in the summer months and improves in winter.

Option D) Lamellar ichthyosis is also a congenital ichthyosis, involving mutations in the TGM1 gene. It is characterized by large platelike darkbrown hyperkeratoses covering the entire body with mild palmoplantar involvement. The extreme spectrum of lamellar ichthyosis is congenital ichthyosiform erythroderma (CIE) which is similar to erythroderma seen in psoriasis.

The given image shows pili torti seen in Menke's syndrome or trichopoliodystrophy or steely hair disease.

Pili torti refers to hair showing 180-degree twists under the microscope. Scalp and eyebrow hair appear short, sparse, lustreless, tangled, and depigmented. Hair changes can be the first sign of disease at 1–2 months of age.

It is an Xlinked recessive disorder. At 2–3 months of age, children with Menke's disease present with:

• Loss of developmental milestones
• Hypotonia
• Seizures
• Failure to thrive
• Cherubic appearance - depressed nasal bridge, pudgy cheeks, ‘cupids bow’ upper lip, and doughy skin.

Option A: In kwashiorkor, hair develops a lustreless, redbrown color that may show alternation with more normal color; this socalled ‘flag sign’ corresponds to alternating periods of significant undernutrition and improved nutrition.

Option B: Selenium deficiency presents as brittle hair and may be associated with exfoliative dermatitis on the scalp.

Option D: In zinc deficiency, hair is dry and brittle, and large areas of alopecia may arise.

The given image shows corkscrew-like hair and the perifollicular purpura, characteristic of vitamin C deficiency or scurvy.

Scurvy develops 1–3 months after a vitamin C deficient diet. The cutaneous manifestations of scurvy include:

• Phrynoderma
• Corkscrew hairs - fractured and coiled hairs due to impaired keratin crosslinks by disulfide bonds
• Perifollicular hemorrhage and purpura
• Lower limb edema
• Splinter hemorrhages

This image shows carotenoderma (of the nose), associated with hypervitaminosis A. Mucous membranes are uninvolved in this condition.

Carotenoderma is a condition associated with hypervitaminosis A. It is characterized by prominent yelloworange pigmentation of the face, palms, and soles of the feet. It can mimic jaundice and medicationinduced pigmentation, but unlike jaundice, carotenoderma spares the mucous membranes.

Discoid lupus erythematosus is a benign inflammatory disorder of the skin, most frequently involving the face and scalp.

It is characterized by welldefined red, scaly patches of variable size, which heal with atrophy, scarring, and pigmentary changes. The circumscribed or discoid form is the most frequent type of disease and occurs particularly on the cheeks, bridge of the nose, ears, side of the neck, and scalp.

The image below shows a localized discoid lupus erythematosus of the scalp with follicular plugging.

The image shows hyperkeratosis and plugging of the follicular ostia with keratotic material, otherwise known as the carpet tack sign or tin- tack sign, or cat's tongue sign, seen in discoid lupus erythematosus.

In cutaneous lupus erythematosus or discoid lupus erythematosus, the skin lesions present as well-defined erythematous patches with adherent scaling and peripheral hyperpigmentation. When the scale is removed its undersurface shows horny plugs that have occupied dilated pilosebaceous canals. This is called the ‘tintack’ sign.

The clinical scenario along with the image showing discoid lesions on the face with central scarring and active erythematous margins with adherent scales are suggestive of discoid lupus erythematosus. Scarring type of alopecia is seen in discoid lupus erythematosus (DLE).

Histology of DLE shows lymphocytic interface dermatitis with basal layer degeneration, follicular plugging, dermal mucinosis, and epidermal atrophy.

The first-line treatment for localized lesions is topical corticosteroids.

Hydroxychloroquine and chloroquine are oral antimalarial drugs that can be used along with oral steroids and have a good response rate.

Subacute cutaneous lupus erythematosus presents most commonly as a nonscarring papulosquamous eruption. It can also present as annular polycyclic lesions.

Sites of lesions:

• Above the waist
• Around the neck
• On the trunk
• Outer aspects of the arms

The image below shows psoriasiform lesions of subacute cutaneous lupus erythematosus.

The most common cutaneous manifestation of systemic lupus erythematosus is photosensitivity. In decreasing order, the cutaneous manifestations in SLE are:

• Photosensitivity
• Raynaud's phenomenon
• Malar rash
• Chronic urticaria gt;36 hrs
• Non-scarring alopecia
• Mouth ulceration