Tutorial 3

 

These tutorials are particularly directed at third and fourth year registrars. They are meant to give you a broad introduction to clinical dermatology particularly aspects of differential diagnosis. They will use online atlases ,PubMed and eMedicine websites as resource materials as well as the cases in the Dermconsult website itself. The format is based on one used by Ken Paver some years ago.

Search eMedicine          Search Perplexity AI

Topics covered in this tutorial

1. The DD of papules.
2. Eyelid papules.
3. Acral papules.
4. Oral papules
5. Yellow papules
Questions will also be asked on the following disorders-

Lymphomatoid papulosis.
Sarcoidosis.
Pseudoxanthoma elasticum
Lipoid proteinosis
Lichen amyloid


The Diagnosis of Papular Diseases

These are probably best diagnosed by dividing them into papules on certain sites, papules with certain colours and papules with certain patterns. 

 The sites are namely the eyelids, the mouth, acral and follicular. The colours are yellow, blue black and skin coloured and the patterns are linear, circinate, single, multiple, symmetrical, those associated with bullae, scaling and non scaling.

Oral Papules The differential diagnosis includes oral florid papillomatosis, Darier's Disease, tuberous sclerosis, Cowden's Syndrome, acanthosis nigricans, multicentric reticulo histiocytosis, lipoid proteinosis, Goltz Syndrome, Heck's Disease.

Eyelid Papules Naevi, warts particularly mollusca, syringomas, sarcoidosis,  acnitis, amyloidosis, See this case of lipoid proteinosis.

Acral Papules Warts, acrokeratosis verruciformis, epidermodysplasia verruciformis, Gottron's papules, multicentric reticulo histiocytosis, sarcoidosis, lichen planus, granuloma annulare.

Asymptomatic labial papules in a teenager

The photo below is of lymphomatoid papulosis

Syndromes with Acanthosis Nigricans

These include Prader Wili, Sjogren Larsen, Rudd's, Down's, Lawrence Seip,  Leprechaunism, Wilson's Disease, Polyendocrine Syndrome. In the benign form of acanthosis nigricans most patients show features of obesity and insulin resistance. The malignant form of AN is far less common, and, in one study, only 2 of 12,000 patients with cancer had signs of AN.

GlobalSkinAtlas Acanthosis nigricans  eMedicine-Acanthosis nigricans eMedicine-Lawrence-Seip Syndrome

Symmetrical black plaques on the toes

Syndromes with Poikiloderma

The list includes Rothmund Thompson Syndrome, Bloom's Syndrome, Cockaynes, Dyskeratosis Congenita, Erythropoietic Proto Porphyria and Werner's Syndrome.

The age of onset of the poikiloderma is a good way of separating out these conditions.

Syndrome	Typical onset of poikiloderma	Key associated features in children	Malignancy risk
Rothmund–Thomson syndrome (poikiloderma congenitale, RECQL4)	Facial rash in infancy, evolving to poikiloderma by 3–5 yearsncbi.nlm.nih+1	Short stature, sparse hair/eyebrows, photosensitivity, juvenile cataracts, skeletal anomalies (radial/thumb defects, bone dysplasia), dental anomalies, GI symptoms, hypogonadism, possible developmental delaylink.springer+2	High risk of osteosarcoma in late childhood/adolescence and non‑melanoma skin cancers; other internal malignancies reportedonlinelibrary.wiley+1
Kindler syndrome (KIND1/FERMT1)	Poikiloderma appears in early childhood after infancy blisteringpmc.ncbi.nlm.nih+2	Acral trauma‑ and photosensitive blistering in infancy, photosensitivity, progressive poikiloderma on photoexposed sites, skin atrophy, mucosal fragility, strictures (oral, esophageal, urogenital), periodontitispmc.ncbi.nlm.nih+1	Increased risk of cutaneous squamous cell carcinoma in adulthood reportedjamanetwork
Poikiloderma with neutropenia (C16orf57/USB1)	Early childhood poikiloderma, often first years of lifeonlinelibrary.wiley+1	Chronic neutropenia with recurrent sinopulmonary and skin infections, nail dystrophy, palmoplantar hyperkeratosis, short stature, facial dysmorphism; bone marrow failure may evolvemedlineplus	Elevated risk of myelodysplastic syndrome and acute myeloid leukemiaonlinelibrary.wiley+1
Dyskeratosis congenita (telomere biology disorders)	Childhood or adolescent poikiloderma, often reticulated pigmentation on neck/upper chestonlinelibrary.wiley+1	Classic triad: abnormal reticulated pigmentation, nail dystrophy, oral leukoplakia; plus bone marrow failure, pulmonary and hepatic fibrosis, developmental delay in some subtypessciencedirect	High risk of bone marrow failure, myeloid malignancy, solid cancersonlinelibrary.wiley+1
Hereditary sclerosing poikiloderma (Weary type and related)	Early childhood onsetsciencedirect+1	Generalized or acral poikiloderma with progressive dermal fibrosis/sclerosis, flexion contractures, possible tendon/ligament involvement; usually little systemic malignancy risk reportedsciencedirect	Malignancy risk less well defined; not a classic cancer‑predisposition syndromeonlinelibrary.wiley+1
Hereditary fibrosing poikiloderma (e.g. POIKTMP/FAM111B)	Infancy/early childhood poikilodermaonlinelibrary.wiley+1	Progressive poikiloderma, tendon contractures, myopathy, lipodystrophy; systemic fibrosis may involve lungs, pancreas, and other organsonlinelibrary.wiley	Data limited; some reports of internal organ dysfunction rather than frank cancer predispositiononlinelibrary.wiley

Chronic plaques in a patient with ataxia telangiectasia

The photo below illustrates acanthosis nigricans on the neck  Click here to view this case

Cowden's Syndrome

In this condition there are often pearly papules on the palms and soles with also papules at the side of the lips and tricholemmonas on the face. This syndrome is associated with internal malignancies, particularly of the breast and thyroid. Note-If you see a patient with what you think are warts on the face have a close look at their gums and see if there are verrucous lesions there. Then look more carefully at the skin for lipomas, fibromas lymphangiomas and angiomas. The warty lesions on the skin will be trichilemmomas.

Other Central Facial Papules

Multiple trichilemmomas        Image
Multiple trichilemmomas
Adenoma sebaceum (multiple angiofibromas)
Darier disease
Syringomas (usually located under eyes as opposed to perinasally)
Fibrofolliculomas (in Birt-Hogg-Dube syndrome)    Image
eMedicine-Cowden's Syndrome
Multiple facial papules in an adult

Trichoepithelioma

Trichoepithelioma is a skin coloured papule found on the nasal labial folds and eyelids. It is worse at puberty. This should be compared with tuberous sclerosis which is better at puberty. Trichoepitheliomas are often found in association with cylindromas. It is due to the presence of an autosomal dominant gene on chromosome 9 which can show dimorphism and variable penetration. Linear and dermatomal forms of trichoepithelioma may sometimes be seen as well as a variant with a large hemifacial plaque.

eMedicine-Trichoepithelioma         Image

The photo below is a solitary desmoplastic trichoepithelioma

Lichen Amyloid

Lichen Amyloid is a papular disorder seen particularly on the lower limbs with the pathology being in the lower dermis. This can be compared with lichen myxedematosus where the lesions are usually seen in the upper limb and the pathology is in the upper dermis. The lesions of lichen amyloid are brown, slightly scaly, discrete papules but often they will join up to form infiltrated plaques, particularly over the shins. They are usually very itchy. The papules of lichen myxedematosus are often waxy, dome shaped or flat topped papules. They also can coalesce into plaques and linear forms are known.

GSA Lichen Amyloidosis      eMedicine-Lichen Amyloid

Skin induration with multiple flesh coloured papules

Kyrle's Disease

These are hyperkeratotic papules up to 1 cm in diameter with confluence sometimes producing polycyclic plaques. It spares the palms and soles. It is found especially on the legs in the 30 to 60 year age group.

eMedicine-Kyrle's Disease        Image

Question: Are mucosal lesions present in lichen myxedematosus?

Answer: Mucosal lesions are absent in lichen myxedematosus

The photo below is lichen amyloidosis

Itchy hyperkeratotic papules particularly on the lower legs

Lipoid Proteinosis

Note that this condition is often seen at birth and is associated with hoarseness in the newborn baby. This is due to an infiltrate in the vocal chords. The lesions typically affect the oral mucosae. The tongue is often like wood. Eyelid papules are commonly seen in this condition.

Globalskinatlas- Lipoid Proteinosis          eMedicine-Lipoid Proteinosis

Buschke-Ollendorff Syndrome

Buschke-Ollendorff Syndrome is an autosomal dominant disorder with widespread dermal papules and plaques, mainly asymmetrically on the trunk and limbs. Osteopoikilosis is seen in the long bones. Connective tissue naevi are also seen in tuberous sclerosis and because at least 50% of cases of this condition are new mutation, every patient with a connective tissue naevus should be checked for evidence of tuberous sclerosis.

eMedicine-Buschke-Ollendorf Syndrome         Image

Widespread pea sized papules and gooseflesh plaques in a 44 years old woman

Question 1: What skull x-ray features are pathognomonic for lipoid proteinosis?

Question 2: Early stage lipoid proteinosis may produce bullae and pustules which heal with acne like scars. What other condition may this simulate?

Question 3: What two features are common to both tuberous sclerosis and lipoid proteinosis?

Answer 1: Sickle-shaped calcifications found dorsal and lateral to the sella turcica in skull x-rays are pathognomonic.

Answer 2: Erythropoietic Protoporphyria.

Answer 3: Both have cerebral calcification and papules on the eyelids.

Angiofibromas of tuberous sclerosus

Periungual fibroma

Cutaneous fibroma plaque

Sarcoidosis

The skin involvement of sarcoid is either specific showing granulomas on histology or non-specific, mainly reactive such as erythema nodosum. Skin lesions appear before systemic disease in 20% of cases, there is a simultaneous appearance in 50% and in 30% the skin lesions may occur up to 10 years after the systemic disease, often when oral steroids are withdrawn in pulmonary sarcoidosis. Papular sarcoid is particularly common on the face.

Global Skin atlas - Sarcoidosis              eMedicine-Sarcoidosis

Off-Centre Fold Recurrent Pruritic papules in a 74 years old man An Unusual cause of hair loss Erythroderma in a patient with arthritis,uveitis and dyspnoea Hypopigmentation of the extremities

The photo below is annular sarcoidosis 

Small sarcoidal papules looking like granulomatous rosacea

Question 1: What are the various patterns of sarcoidosis and where may they be found?

Question 2: What systemic features may be seen with lupus pernio?

Question 3: Do you get sarcoidosis in the mouth?

Answer 1: Annular - the face and forehead.
Papular - the face
Nodular - the trunk
Angiolupoid - the eyelids
Chilblain-like - the ears, the nose, the cheeks
Scar like - needless to say in scars
Ulcerative - on the legs
Hypopigmented - on the trunk
Erythrodermic - all over the body
Ichthyosiform - particularly the trunk
Alopecia - obviously the scalp
Answer 2: 75% of cases have respiratory tract involvement, 40% have granulomas in bones with punched out cysts, generally on the fingers. Eye lesions occur in about 40% of cases.

Answer 3: Yes, there may be pinhead sized papules, particularly on the hard palate, tongue and buccal mucosa but they may coalesce to form a plaque.

Yellow Papules

Yellow Papules

A mnemonic for yellow papules is SEXI Grannies. S stands for sebaceous, E for elastotic disorders, X for xanthomas, I for infiltrates, particularly lipoid proteinosis, lichen amyloid, EPP and colloid milium. Grannies stands for granulomas.

GSA - Pseudoxanthoma elasticum                eMedicine-Pseudoxanthoma elasticum

Multiple light yellow papules

Pseudoxanthoma Elasticum

The photo below is of colloid milium.The pale area has been lasered with a CO2 laser.

Question: What are angioid streaks?

Answer: They are breaks in the elastic membrane of Bruch at the back of the eye. Eight five percent of PXE patients will show these. These lesions appear earlier than the skin changes and may be the only sign of the disease for years. Angoid streaks are not diagnostic for PXE and may be seen in several other skin diseases and Paget's Disease of bone and Sickle Cell Disease. The papules in PXE are yellowish to cream coloured, the skin is crepe like, lax with redundant folds, the so-called plucked chicken skin. It is often seen on the neck or the inside of the upper arms.

Cowden's Syndrome

Trichilemmomas are a specific cutaneous marker for Cowden's Syndrome. These lesions particularly occur on the head and neck. Patients with Cowden's Syndrome have a marked increase in carcinoma of the breast, thyroid and colon. Other benign features include acral keratotic papules and oral mucosal papules.

Multiple facial papules in an adult

The photo below is of perifollicular fibromas

Question: How would you differentiate histologically between a fibro folliculoma and a perifollicular fibroma?

Answer: In fibro folliculoma there is proliferation of the follicular epithelium as strands extending into a well circumscribed mantle of connective tissue. In perifollicular fibroma the hair follicle is generally unaltered but the follicles are surrounded by a concentric arrangement of collagen fibres. Both lesions are seen in the autosomal dominant disorder known as the Birt-Hogg-Dube Syndrome. Individuals with this syndrome and their relatives should have abdominal tomography for renal cancers, ultrasound screening for renal tumours

Lymphomatoid Papulosis

These lesions usually occur in crops anywhere on the body. There may be very few lesions. The lesions are similar to those of pityriasis lichenoides et varioliformis acuta except that they have a greater tendency to necrosis. Some of the lesions have a tendency to heal spontaneously. The lesions often heal with scarring.

GSA - Lymphomatoid Papulosis        eMedicine-Lymphomatoid Papulosis

Red nodules on the arm of a patient with breast cancer

The photo below is lymphomatoid papulosis .This subsequently evolved into a CD 30 positive T cell lymphoma 

Question: What is the most common associated lymphoma with lymphomatoid papulosis?

Answer: Mycosis fungoides in 40% a CD 30-positive T cell lymphoma in 30% and Hodgkin's Disease in 25%. Note that the presence of clonal rearrangement in lymphomatoid papulosis lesions is not predictive of the behaviour of that lesion or the case in general.

What are the skin signs of Dermatomyositis?

Periocular violaceous erythema with ragged cuticles and periungual capillary dilatation. There are often violaceous papules on the legs like lichen planus and erythema, particularly on the dorsal surfaces of the knees and elbows. Photo sensitivity is often seen. Calcification occurs particularly in children.

A patient with dermatomyositis and linear streaks on the back Dermatomyositis-Practical aspects

Finger Pulp Ulcers and Scars

These can be due to Raynaud's Disease, perniosis, scleroderma, systemic lupus, cryoglobulinemia, rheumatoid arthritis and sub acute bacterial endocarditis.

Cause category	Key mechanisms / examples	Notes / typical context
Poor blood flow (digital ischemia)	Raynaud’s phenomenon, prolonged vessel narrowing, ischemia of fingertip skin	Fingers may change colour with cold or stress; can progress to “digital” ulcers.
Systemic sclerosis / scleroderma	Scarring and narrowing of small arteries, recurrent tip ulcers	Often very painful ulcers at tips or under nails; common in scleroderma.
Trauma and pressure	Repetitive minor trauma (tapping, tools, instruments, sports, biting/picking)	Dry or thin skin splits; in poor circulation, small injuries become chronic ulcers.
Infection	Paronychia, felon, infected hangnails, other local finger infections	Can ulcerate if untreated; recurrent infections may leave pitted or thickened scars.
Connective tissue / vasculitic disease	Lupus, rheumatoid arthritis, vasculitis affecting small vessels	Vessel inflammation and occlusion → fingertip ulcers, sometimes in multiple digits.
Metabolic / vascular risk factors	Diabetes, smoking, high blood pressure, high cholesterol	Microvascular disease and poor healing increase ulcer risk and delay recovery.
Occupational / chemical exposure	Irritants (detergents, solvents), wet work, vibration tools	Skin cracking and splitting, Raynaud-like changes in some workers using vibrating tools.
Neurological / behavioural factors	Neuropathy (numbness), habitual picking or self-injury	Injuries go unnoticed or are self-inflicted, become chronic wounds and scars.

Ragged cuticles of dermatomyositis

Tutorial 21

 Topics discussed in this Tutorial

Compare Alopecia areata, trichotillomania and traction alopecia

Cutaneous calcification

Pachyonychia congenita

Skin lesions in Hogkin's lymphoma

Eyelid papules

Genitocrural candidiasis

Clinical features of Lipoid proteinosis

Ichthyosis with mental retardation

Punctate keratodermas

Ichthyosis on the face

Compare alopecia areata, trichotillomania and traction alopecia.

Alopecia areata can occur in all age groups. There is a bald area with complete loss of hair follicles but preservation of the follicular openings.

In trichotillomania in adults it is usually occipital, in children it is temporal opposite to the handedness. Also adults tend to close crop the hair whereas in children it is left with very irregular lengths, which point irregularly in all directions.

In traction alopecia it usually is due to the hair being pulled up into a bun and it gives an ophiasis like pattern. If mainly affecting the frontal scalp it can look like frontal fibrosing alopecia. Other types of traction alopecia include marginal which is usually the forehead. Hot comb which involves the crown then spreads centrifugally (now called central centrifugal cicatricial alopecia) and the massage type alopecia.
Pressure alopecia occurs after surgery or in the neonatal period particularly on the occipital scalp.

The image below is of Trichotillomania

Cutaneous Calcification

This is usually considered under the headings of dystrophic, metabolic, idiopathic and normocalcemic. Dystrophic is just localised injury due to trauma or inflammation. It can occur in degenerative processes such as pseudoxanthoma elasticum and also in benign and malignant neoplasms.

Metabolic calcification is found with hyperparathyroidism and sarcoidosis, vitamin D intoxication, the milk alkali syndrome or in destructive bone disease seen in myeloma and Paget’s disease of bone.

Idiopathic calcification can be due to calcinosis universalis, which is a primary disorder seen in girls and young children where sinuses may develop. Other forms are cutaneous calculus, pinnal calcification and tumoral calcinosis. Universal calcification can be a secondary feature of dermatomyositis, scleroderma, lupus and acrodermatitis chronica atrophicans.

Normocalcemic cutaneous calcification is seen in chronic renal failure and pseudo hyperparathyroidism.

Pineal calcification occurs in Addison’s disease, ochronosis, acromegaly, dermatomyositis, hyperthyroidism, systemic chondromalacia and familial cold hypersensitivity.

Hypocalcemic calcification causes dry skin, alopecia, brittle nails that are grooved. You may have chronic mucocutaneous candidiasis.

Intravenous Bleomycin and calcium gluconate injections can give localised calcification.

The image below is of Calcification in Scleroderma

Pachyonychia Congenita

This can look like large corns on weight bearing areas with the plantar keratoderma.

Adolescent striae obviously presents in adolescents. The site of choice is usually the lumbo sacral area in boys whereas in girls it is the breasts and hips.

Question

What are the skin lesions of Hodgkin’s disease?

Answer

They are often non-specific in 30% to 50% of cases and include pruritus, prurigo, herpes zoster, addisonian pigmentation particularly in the axillae, groins and nipples.

The image below is of Pachyonychia Congenita

Causes of Eyelid Papules

They include acnitis, syringomas, molluscum, amyloid, lipoid proteinosis, sarcoidosis, rosacea, Fabry’s disease and trichoepitheliomas. Most trichoepitheliomas are skin coloured or yellow or pink. They can occasionally be bluish because of pigment. The inheritance is probably autosomal dominant but there are more females than males.

The image below is of Syringomas

What are the types of genitocrural candidiasis?

Answer

Firstly there is the intertrigo like, then there is a pustular type, and also an erosive type on the scrotum. There is an ulcerating type and there is a balanitis type on the penis. Around the perianal and natal cleft candida looks like psoriasis and there is the rare granulomatous type of candidiasis seen in neonates.

The image below is of groin candidiasis.

What are the clinical features of lipoid proteinosis?

Answer

Hoarseness with thickening and stiffening of the tongue, eyelid papules and papules on the hands. The nodular lesions on the elbows look like xanthomata.

The image below is of eyelid papules in lipoid proteinosis.

Adolescent striae obviously presents in adolescents. The site of choice is usually the lumbo sacral area in boys whereas in girls it is the breasts and hips. What are the other causes of striae? Answer Pregnancy, drugs, collagen diseases and Cushing’s disease. Note that there are no striae with Ehler’s Danlos patients when they are pregnant.   You can get a rare horizontal striae on the nose in children under 10 with a defined ridge on the bridge of the nose, which is related to the growth of underlying structures. It just disappears. The image below is of steroid induced striae.

What are the causes of ichthyosis with mental retardation? Answer X-linked ichthyosis sometimes, Sjogren Larsen, Rudd’s syndrome, Richner Hanhart syndrome and Downs syndrome. The image below is X linked ichthyosis What are the causes of punctate keratoderma? Answer In an infant it is the Richner Hanhart syndrome. In an adolescent it is disseminated punctate keratoderma and Darier’s disease is usually seen in adults though it is variable. Ichthyosis on the Face In ichthyosis vulgaris the face involvement includes the forehead, cheeks and scalp. In X-linked ichthyosis it tends to involve the periphery of the face. The image below is of X linked ichthyosis.