Tutorial 7

These tutorials are particularly directed at 3rd and 4th 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 and Off-Centre Fold cases from the Archives. The format is based on one used by Ken Paver some years ago.

Search eMedicine Topics covered in this tutorial

Causes of localised and generalised hyperpigmentation.
A newborn with hard firm skin
Conditions with a scaly serpiginous edge
Ichthyosis and mental retardation
Nodules in vets and farm workers.

Questions will be asked on the following topics:

Acrodermatitis enteropathica
Monilethrix and
Giant Condyloma of Buschke



Generalised and Localised Hyperpigmentation

The mnemonic to use for this is DAMN and ANNE. 

 For generalised hyperpigmentation it is DAMN with D for drugs, such as Bleomycin, Gold, Arsenic and Cyclophosphamide. A for autoimmune - for example lupus dermatomyositis and scleroderma, M for metabolic - particularly hemochromatosis, renal failure, hepatic failure, malabsorption, PCT and amyloid, N for neoplastic - particularly lymphoma, melanoma and carcinoma and E for endocrine - particularly Addison's Disease, acromegaly, thyrotoxicosis and phaeochromocytoma.

Localised hyperpigmentation use the mnemonic ANNE. The autoimmune being the same as generalised, neoplastic also, another N for nutritional - for example pellagra and malabsorption and E for endocrine as in generalised.

Sometimes it is easier to consider what causes skin hyperpigmentation and work back from there. eg Melanin in melanomas and post inflammatory hyperpigmentation, iron in blood in the pigmented purpuric dermatoses, drugs and chemicals as in argyria and excess stimulation of melanocytes from ACTH and other hormones in the endocrine disorders.

eMedicine-Incontinentia pigmenti

eMedicine-Dermatopathia Pigmentosa Reticularis

eMedicine-Pellagra

Cutaneous reactions to cytotoxic drugs Acral erythema and peeling is one of the commonest cutaneous reactions occurring with cytotoxic drugs. See link for some of the newer biologics.

The image below is a plant contact dermatitis Lime Phytophoto dermatitis

Newborn with Hard, Firm Skin

The three things to consider are neonatal cold injury, sclerema of the newborn and subcutaneous fat necrosis of the newborn.
Neonatal cold injury

Babies are usually healthy. It occurs within the first 24 hours. The skin is red or purple with pitting oedematous extremities. The rest of the body is white and cold. There can be a 25% mortality mainly from pulmonary haemorrhage.

Sclerema of the Newborn

It is usually a premature baby who is ill. It occurs on the buttocks and trunk but spreading then peripherally. Compare this with neonatal cold injury. There is no pitting. The skin has a yellow white colour. The palms and soles and the genitalia are usually spared. The onset is early. There is a 50% mortality.eMedicine-Sclerema neonatorum

Subcutaneous Fat Necrosis of the Newborn

Again the baby is usually healthy. The onset is in the first 2 to 20 days with variable size and number of violaceous nodules. Some babies have hypercalcemia and the complications of this. Histology will often show granulomatous inflammation in the fat whereas the histology of sclerema of the newborn shows very little. Generally this condition will clear up on its own. Some nodules may rupture and scar.

eMedicine-Subcutaneous Fat necrosis of the Newborn

An infant with firm fixed plaques

The image below is sclerema neonatorum

Conditions with a scaly serpiginous edge

Necrolytic migratory erethyma
Subcorneal pustular dermatosis

Hailey Hailey Disease, and 

Pemphigus Foliaceus      Image

Larva migrans gives a very typical serpiginous rash but it is not scaly       Image

Recurrent annular erythematous scaly patches

The image below is necrolytic migratory erythema

Nodules in Vets and Farm Workers

Orf. Orf is a red papule initially but it is umbilicated later. It may be target like and pseudo bullous.

Milker's nodules. This condition goes through the same developmental stages as Orf before resolving over a five to six week period. It can be difficult to tell the two apart clinically, and Cowpox presents as vesicles and umbilicated pustules. Person to person contact is possible and it does give protection against smallpox.     Image
Consider also deep fungal infections and atypical mycobacterial infections.

Cutaneous manifestations of biological warfare agents

The image below is of multiple orf

Ichthyosis with Mental Retardation

Netherton's Syndrome. This gives an annular rash called ichthyosis linearis circumflexa. This causes a double edged scale. It also gives bamboo hairs , a hair shaft abnormality, called Trichorrhexis Invaginata.
eMedicine-Netherton's syndrome        Image

Down's Syndrome with X linked ichthyosis and ichthyosis vulgaris.
Sjogren-Larssen. This gives an ichthyosiform erythroderma.eMedicine-Sjogren-Larsson syndrome
Rudd's Syndrome which also gives an ichthyosiform erythroderma and
Conradi's Syndrome which gives a whorled ichthyosis but has an ichthyosiform erythroderma at birth. Look also for stippling of the bony epiphyses.
Abnormal hair growth in a child with atopy      Neonatal and infantile erythrodermas

The image below is of ichthyosis linearis circumflexa

Acrodermatitis Enteropathica

This is a vesiculo bullous rash that may present just with crusting or a spreading scaly rash around the perineum and also around the mouth and cheeks. It usually occurs in premature babies or in other children at around weaning time. Paronychia may occur as well as loss of scalp hair, eyebrows and eyelashes. Secondary infection with staph aureus and candida is not uncommon. Acrodermatitis enteropathica can be an autosomal recessive disorder but obviously there is the acquired type as well. Clinically they appear the same. The differential diagnosis includes atopic dermatitis, psoriasis, seborrhoeic dermatitis, Kwashiorkor, cystic fibrosis, Glucagonoma Syndrome, essential fatty acid deficiencies, mucocutaneous candidiasis, histiocytosis X, neonatal lupus erythematosus, epidermolysis bullosa, biotin and multiple carboxylase deficiencies and other conditions causing acquired zinc deficiencies. This is an interesting differential diagnosis list and is well worth going through these conditions thinking about how their presentation would differ from that of acrodermatitis enteropathica.

eMedicine-Acrodermatitis enteropathica

Periorificial dermatitis and irritability in an infant

The image below is acrodermatitis enteropathica

Glomus Tumours

The solitary glomus tumour is a small blue red papular nodule that may be soft or firm but is usually painful. Temperature changes can cause pain to occur. It is commonly seen in the nail beds, however it has also been reported on the neck, face, penis and scrotum.

In contrast, multiple Glomus tumours are usually asymptomatic but occasionally are painful and they are typically found in children. They can be inherited in an autosomal dominant manner. The Kasabach-Merritt Syndrome (consumption coagulopathy) can be seen rarely in patients with generalised multiple Glomus tumours. Histologically there are fewer glomus cells in multiple Glomus tumours and they are not encapsulated.

eMedicine-Glomus tumour

Diffuse and progressive nodular plaques

Monilethrix

In monilethrix the lanugo hair at birth may be normal but is soon replaced by dry brittle lustreless hair which breaks easily. If the hair shafts are examined they show nodes 1mm apart with intervening tapered non-medullated constrictions. A string of beads appear and this is what gives the condition its name. Monile is the Latin for necklace and thrix is the Greek for hair. People with this condition seldom need a haircut because the hair breaks. There is often associated follicular hyperkeratosis and keratosis pilaris of the scalp and arms and cheeks can also be seen. The condition is inherited as an autosomal dominant.

Pseudo monilethrix

Pseudo monilethrix shows nodes as well, but these are actually indentations in the shaft of the hair. These indentations occur at irregular intervals. It is thought to be due to inadvertent mechanical pressure. A hair mount showed the irregular nodes in pseudo monilethrix.

eMedicine-Monilethrix

Unraveling the genetics of hair and nail genodermatoses

eMedicine-Giant condyloma of Buschke

An ulcerating verrucous plaque on the foot

The image below is Giant condyloma of Buschke

Question 1. What pigmentation pattern may occur with Doxorubicin?

Question 2. What 2 important cutaneous reactions can occur with Hydroxyurea?

Question 3. What type of pigmentation can occur with Bleomycin?

Question 4. What are the histology findings in sclerema neonatorum?

Question 5. Is Necrolytic migratory erythema always seen with a glucagonoma?

Question 6. In Netherton's syndrome the hair and skin abnormalities may not develope until after the first year of life.What hairs may give you the diagnosis first?

Question 7. Can acrodermatitis enteropathica be seen in full term breast fed babies?

Question 8. Multiple glomangiomas occur at an earlier age than solitary lesions T or F?

Answer 1. melanotic macules may appear on the trunk or extremities.

Answer 2. Leg ulcers and lichenoid poikilodermatous reactions.Also dermatomyositis like on the dorsum of the hands.

Answer 3. Flagellate pigmentation.

Answer 4. Oedema, a thickening of the subcutaneous fibrous septa, and a radial array of fine needlelike clefts in the fat cells. The fat cells often are enlarged. In contrast to subcutaneous fat necrosis of the newborn, no fat necrosis or inflammation exists.

Answer 5. No. Cases have been seen in the abscence of a glucagonoma but in association with chronic liver disease, chronic pancreatitis, traumatic necrotizing pancreatitis, celiac disease, and jejunal adenocarcinoma.

Answer 6. The eyebrow hairs.Reference

Answer 7. Yes There may be low zinc levels in some mother's breast milk.

Answer 8. True Multiple glomangiomas present at an earlier age than do solitary lesions, with one third presenting before the age of 20 years. Solitary tumors occur equally in both sexes, whereas multiple tumors are more frequent in males.

Tutorial 12

Topics discussed in this Tutorial

White spots DD

Papular dermatitis childhood DD

Localised hyperpigmentation

Congenital localised hyperpigmentation

Lipoatrophy and Lipodystrophy

Granulomas with scars

Violaceous coloured face DD

Compare pemphigus foliaceous, vulgaris and Pemphigoid

 Differential Diagnosis of White Hypopigmented Spots

This is a difficult differential. Using the SIGN DIP mnemonic, the main Squamous diseases are psoriasis, pityriasis rosea, pityriasis lichenoides and pityriasis Alba. The infective ones are syphilis, pinta and leprosy, granulomatous is sarcoid, neoplastic is halo nevus. Drugs are various hypopigmenting chemicals such as phenols. The immunological inflammatory diseases are lichen sclerosis , morphea, scleroderma, lupus and the Vogt-Koyanagi syndrome. Physical causes are radiodermatitis, and idiopathic guttate hypomelanosis. Remember also Degos syndrome and Albo papuloid epidermolysis bullosa.

The image below is pityriasis alba.

The differential diagnosis of papular dermatitis in childhood includes the Gianotti-Crosti syndrome. Juvenile papular dermatitis, which is like Gianotti-Crosti but there is no liver involvement, lymphadenopathy and there are discreet lichenoid lesions on the hands and forearms. There is also a frictional lichenoid eruption of childhood, which is on the knees and the back of the hands. Caterpillar dermatitis, mites and scabies can all cause a papular dermatitis. This image is of the Gianotti- Crosti syndrome Localised hyperpigmentation. It is difficult to get an encompassing Mnemonic that works! Clinically look out for fixed drug reaction and localised scleroderma or the Pasini Pierini variant of morphoea.  Image The mneumonic we used is DAMN PIG PAPA . D for drugs, A for autoimmune, M for metabolic diseases such as ochronosis and N for neoplastic including metastases and mast cell tumours. P is for post inflammatory, I was infective causes and G was granulomatous diseases. The PAPA is P for parapsoriasis, A for amyloid, P for pigmented purpuric dermatosis and the other A for acanthosis nigricans. The image is of a fixed drug reaction.    Congenital localised hyperpigmentation. If multiple spots it was the Peutz-Jeghers syndrome, urticaria pigmentosa or the leopard syndrome. If it occurred in a patterned form it was incontinentia pigmenti, Albright’s disease and Fanconi’s syndrome. If there were café lait spots it was neurofibromatosis, Albright’s or Gaucher’s syndrome. Naegeli’s syndrome is like incontinentia pigmenti but with no previous inflammation. The image is a case of mastocytosis Localised Lipoatrophy can be annular lipodystrophy or post inflammatory, for example after leprosy, lupus or scleroderma. It can be due to drugs such as insulin and corticosteroids. It can be nevoid. The other drugs that commonly cause Lipo atrophy are the drugs used to treat AIDS. HAART drugs commonly cause this problem. Lipodystrophy presents either as a depression, lipoatrophy , or as an induration of the skin. Lipohypertrophy is due to changes in the subcutaneous tissue. Some of the cases of Lipoatrophy associated with HAART have seen a redistribution of subcutaneous fat with accumulation of fat in abdominal and cervical areas. Some 25% to 50% of patients taking HAART drugs develop some form of Lipo dystrophy. Protease inhibitors reduce fat formation in a dose responsive manner. The most common form of Lipoatrophy probably follows the various types of panniculitis. Remember some of the acquired partial Lipodystrophies can be associated with a reduction in the C3 level and with nephritis. Lipohypertrophy can be due to repeated injections of insulin. Normally we think of insulin causing some degree of Lipoatrophy. It is independent of the type of insulin used. Growth hormone injections have also caused Lipohypertrophy. Rotating injection sites tends to stop the Lipohypertrophy forming. Total fat atrophy can occur in a congenital form when it usually is before the age of two with hepatomegaly, xanthomata, an increase in bone growth and an insulin resistant diabetes. In adults when it occurs there is often acromegaly but no hepatomegaly and they may well show acanthosis nigricans as a measure of some insulin resistance. A degree of fat atrophy commonly occurs in scleroderma and there is the Parry Romberg variant when you get facial hemiatrophy. See Dermnet on Morphoea  Fat atrophy from HAART drugs Lupus Vulgaris It presents as a granuloma with scars. The diffuse edge shows that it is not a neoplastic disorder. On the legs it may look like psoriasis but it has scars. What are the various tuberculids? See Dermnet on Cutaneous TB The image is of lupus vulgaris Compare pemphigus foliaceus, pemphigus vulgaris and pemphigoid. Pemphigus foliaceus is usually in age groups of less than 60. Involves the chest and the face, slow with scaling and crusting and spreads to the upper body, mucous membrane involvement is uncommon. Pemphigus vulgaris is also in the less than 60 age group. The mouth is commonly involved. It is slow to spread. Presents as erosions and crusts and can go anywhere. Mucous membrane involvement is common. Pemphigoid typically is in over 60 year olds. It begins often in the flexures and can be localised to the leg. It evolves much faster than pemphigus. You tend to have intact bullae, which may be haemorrhagic. It is seen particularly on the trunk and limbs and mucous membrane involvement is uncommon. This is pemphigus foliaceous If you have a violaceous hue on the face what do you consider in the differential diagnosis? Answer You should consider dermatomyositis or porphyria variegata. If it is all over the face consider Cushing’s or porphyria. Always watch for lupus erythematosus and porphyria occurring together and watch the pill aggravating porphyria variegata. The Carcinoid syndrome can cause an intermittent violaceous flushing.