Q1' A man aged 65yrs presents with a 30yr history of severe digital arthritis, sacroiliac joint invo

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The Skin in Systemic Diseases
When you know skin, you know medicine
Professor Malcolm W. Greaves, MD, PhD,
FRCP Visiting Professor in Dermatology Department
of Medicine Universiti Kebangsaan Malaysia
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Q1. A man aged 65yrs presents with a 30yr
history of severe digital arthritis, sacroiliac
joint involvement and scaly plaques on the
extremities and scalp

• What is the likely diagnosis?
• What patterns of arthritis are recognised to
  occur in this condition?
• What nail changes occur typically in this
  disorder?
• Name one common infection recognised to
  exacerbate this condition

Psoriasis
Rheumatoid oligoarthritis symmetric digital
sacriliacspinal arthritis mutilans
Pitting onycholysis
HIV
ref. Moll Wright, Semin. Arthr. Rheum. 3, 55,
(1973)
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Q2. A woman aged 50 yrs presents with a 2 yr
history of progressive tongue enlargement,
associated with a petechial rash on the eyelids
lower abdomen

• What is the probable diagnosis?
• How would you confirm the diagnosis?
• What abnormality would you look for
• a. in the serum
• b. in the urine
• Which internal organs are classically involved?

AL amyloidosis
Rectal biopsy stained with Congo red
radiolabelled SAP
Immunoglobulin light chain
Bence-Jones proteinuria
ref. Falk et al, NEJM 337, 898 (1997)
Kidneys, heart, intestine, peripheral nerves
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Q 3. A 50 yr old man presents with dusky red
facial erythema and periorbital oedema for 3
months and similarly coloured papules on his
knuckles. He has recently had difficulty
climbing his stairs

• What is the probable diagnosis?
• What is the name given to the lesions on the
  knuckles?
• What 2 investigations would you like to do to
  support this diagnosis?
• What underlying disease should be sought in this
  age group?

Dermatomyositis
Gottron,s papules
Serum creatininie kinase Muscle biopsy for
histology
Serum creatinase
Internal malignant neoplasia (Paraneoplastic
syndrome)
ref. Callen, Lancet, 357, 85, (2001)
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Q. 4 A male 21 yr old medical student, recently
returned from an elective in Thailand, presents
with a painful urethral discharge, arthritis, and
lesions on the soles of the feet.

• What is the diagnosis?
• Name one probable aetiological microorganism
• What is the name given to the lesions on the
  soles of the feet?
• Which HLA haplotype is associated with this
  condition?

Reiters syndrome
Chlamydia sp.
Keratoderma blenorrhagicum
HLA B27
ref. Archer et al, Br J Rheumatol, 27,306,1988
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Q 5. A man aged 32 yrs gives a 15year history of
recurrent mucocutaneous swellings, each lasting
around 24 hrs and often associated with abdominal
pain. Some other members of his family have had
a similar problem

• What is the probable diagnosis?
• What blood tests should you do to confirm it?
• What is the mode of inheritance?
• What is an effective treatment in
• the emergency room for a severely affected
  patient?

Hereditary angioedema
Serum complement C4 level (low value positive
screening test), serum C1 inhibitor level (low
value confirms diagnosis)
Dominant
Fresh frozen plasma IV, C1 inhibitor concentrate
IV
ref. Agostoni, Medicine 71, 206 (1992)
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Q6. A 14 yr old boy presents with a 6 day history
of a palpable purpuric rash on the legs with
ankle oedema. He gives a history of a sore
throat 2 wks previously. He is febrile, and has
joint pains and swellings

• What is the clinical diagnosis?
• What is the probable cause in this patient?
• Which other organs are classically involved?
• What is the immunopathological marker in the skin
  in this condition?

Henoch Schonlein purpura
?-haemolytic streptococcal sore throat
Kidneys, intestine
IgA immune complex
ref Tancrede-Bohin et al, Arch Dermatol 133,
438, (1997)
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Q 7. This 18 yr-old boy from Iraq has suffered
severe photosensitivity since birth, with
scarring and digit loss. There is a history of
parental consanguinous marriage. Examination
shows blistering and hypertrichosis, and his
teeth are red.

• What is the probable diagnosis?
• What urinary abnormalities can be expected?
• What is the principal haematological abnormality?
• What is the mode of inheritance?

Erythropoietic porphyria
Urine floresces red on exposure to long
wavelength ultraviolet due to porphyrins
Haemolytic anaemia
Recessive
ref. Fritsch et al. Amer Acad Dermatol, 36,
594, (1997)
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Q 8. A 30 yr-old woman presents with anaemia,
with a blood picture suggesting chronic blood
loss. Examination shows macular pigmentation
around the lips and on the oral mucosa
evidently present since birth, and hereditary.

• What is the likely diagnosis?
• What is the probable cause of the
• anaemia?
• What would be found on endoscopic
• examination?
• What is the mode of inheritance?

Peutz Jeghers syndrome
Intestinal cancer (most commonly duodenal)
Intestinal polyposis
Autosomal dominant
ref. Jenne et al, Nat. Genet. 18, 38, (1998)
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Q 9. A 45 yr-old woman presents with redness,
enlargement and stuffiness of her nose for 9
months. She has also noticed breathlessness on
exertion and a non-productive cough. A CXR shows
changes suggestive of pulmonary fibrosis

• What is the likely diagnosis?
• What would a skin biopsy of the nose show
  histologically?
• Which characteristic laboratory abnormalities are
  likely to be found on routine blood
  investigations?
• What abnormalities are characteristically found
  in X rays of the hands?

Sarcoidosis
Non-caseating granuloma
Raised serum calcium, ACH, ESR, eosiniphilia
Bone cyst
Ref. Jorizzo, J Amer Dermatol, 22,439. (1990))
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Q 10. A 10 yr 0ld girl was prescribed a
sulphomamide for an upper respiratory infection.
4 days later she developed mucocutaneous erosions
round the mouth and a generalised eruption with
flaccid bullae and pyrexia

• What is the probable diagnosis?
• Besides drugs, name two other recognised causes
• What is the most common complication?
• What is the principal histological change in the
  skin?

Steven Johnson syndrome / Toxic epidermal
necrolysis
Virus infection (H. simplex, Mycoplasma) GVHD
Bacterial infection
Epidermal necrosis
Ref. Roujeau, J Invest Dermatol 102, 28s, (1994)
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Q 11. A 45 yr-old man presented with a 4-week
history of painful leg ulceration. He had a past
history of intermittent diarrhoea with mucus,
accompanied by weight loss

• What is the probable diagnosis?
• What is the likely causative underlying disease
  in this patient?
• What other common causes do you know of ?
• What is the first-line systemic treatment?

Pyoderma gangrenosum
Ulcerative colitis or Crohns disease
Rheumatoid arthritis, leukemia, paraproteinaemia,
autoimmune connective tissue disease,
Behcets syndrome
Corticosteroids
Ref. Powell et al, Amer J Med, 55, 173, (1985)
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Q 12. A 38 yr-old housewife, recovering from a
recent stroke, presents with a 2-yr history of
Raynauds phenomenon and a persistent dusky
reticulate-patterned rash on the legs

• What is the name given to the skin changes seen
  on the legs?
• What eponymous syndrome includes all these
  features?
• What serological abnormality is
  characteristically associated with this syndrome?
• What would the classical obstetrical history be
  in this patient?

Livedo recticularis
Sneddons syndrome
Anti-phospholipid antibodies
Recurrent abortion
Ref. Sneddon, Br J Dermatol, 77, 180, (1965)
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Q 13. A 30 yr-old HIV man gives a 4-day
history of persistent shoulder pain, diagnosed by
his GP as arthritic, followed by appearance of
papulovesicles, localised to the same site

• What is the likely diagnosis?
• What is the causative organism?
• What other skin eruption can this agent cause?
• Name an effective systemic treatment

Herpes zoster (shingles)))
Varicella-zoster virus
Chickenpox
Acyclovir, valacyclovir, famcyclovir, foscarnet
Ref. Safrin et al, Ann Int Med 115, 19, (1991)
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Q 14. This 28 yr old woman had multiple nodules
and polypi on the trunk and limbs since
birthand was noted, on routine ophthalmological
examination, to have abnormalities of the irides.
Her son, aged 6, was noted to have several
pigmented lesions on the trunk

• What is the diagnosis?
• What are the eye lesions called?
• What are her sons skin lesions likely to be?
• Name two common non-neurofibromatous internal
  complications

Neurofibromatosis type I
Lisch nodules
CALM (café au lait macules)
Astrocytoma, bony abnormalities including bone
tumours, endocrinopathies including phaechromocyt
oma, hypertension
Ref. Riccardi, NEJM 305, 1617, (1981)
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Q 15. A 50 yr-old man presents with a 2-yr
history of a gradually spreading pruritic
pigmented maculopapular eruption which shows
localised whealing and itching when individual
lesions are rubbed. The patient is otherwise well

• What is the diagnosis?
• How is your diagnosis confirmed?
• What characteristic systemic symptoms may the
  patient develop in future?
• List 3 drugs this patient should avoid

Cutaneous mastocytosis (urticaria pigmentosa)
Histological examination of a skin biopsy stained
with a metachromatic stain e.g. toludine blue to
show increased numbers of mast cells
Flushing, headache, diarrhoea, peptic ulceration,
dyspnoea, bone pain
Opioids, codeine, muscle relaxants,
dye- containing radiocontrast media, aspirin
Ref. Travis, Medicine, 67, 345, (1988)
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Q 16. A boy aged 16 with epilepsy has been noted
to have persistent symptomless papular lesions on
the face since aged 10 yrs. There is a positive
family history

• What is the diagnosis?
• What other characteristic skin lesions may the
  patient have?
• Besides epilepsy, what other characteristic
  internal manifestations may this patient have?
• What are the characteristic skull radiological
  findings?

Tuberous sclerosis
Ash leaf hypopigmented macules periungal
fibromata shagreen patches
Retinal plaques, rhabdomyomas, angiomyolipomas,
polycystic kidney disease
Intracranial calcificaton (tubers, candle
guttering)
Ref. Roach et al, J Chlid Neurol, 7, 221,(1992)
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Q 17. A 45 yr-old woman, previously treated for
thyrotoxicosis, but now not on treatment, has
developed dermal nodules on both lower legs

• What is the diagnosis?
• What associated clinical manifestation is visible
  in most patients?
• What are the main characteristic histological
  findings in involved skin?
• What effect, if any, will thyroid replacement
  therapy have on these skin lesions?

Pretibial myxoedema
Eye changes (proptosis, exophthalmos, lid
retraction)
Dermal deposition of glycosaminoglycans
No effect
Ref. Fatourechi et al, Medicine, 73, 1, (1994)
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Q 18. A woman aged 40 yrs with rheumatoid
arthritis has over a prolonged period received
numerous drugs systemically for this indication.
She now presents with progressive pigmentary
changes on both lower legs and feet

• Which drug, used for this indication, is
  recognised to cause these skin changes?
• Name one other chronic adverse effect which can
  result from long-term administration of this
  compound
• What is the nature of the pigment deposited in
  this patients skin?
• Name 2 unrelated drugs which can cause similar
  pigmentary skin changes

Antimalarial (chloroquine, hydroxychloroquine)
retinopathy
Complex of drug with melanin
Phenothiazines, amiodarone, minocycline, silver
salt
Ref. Tuffanelli, Arch Dermatol, 33, 419, (1963)
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Q 19. A 40 yr-old man presented to the skin
clinic with persistent swelling of the lower lip
which , upon palpation, was indurated.
Examination inside the mouth showed a cobblestone
thickening of the palatal mucosa. He had a
previous history of chronic inflammatory bowel
disease

• What is the probable diagnosis?
• What are the histological appearances of a skin
  biopsy in this condition?
• What other mucocutaneous manifestations are
  recognised to occur commonly in this condition?
• What other condition closely mimics the oral
  muco-cutaneous and histological changes occuring
  in this patient?

Crohns disease
Non-caseating granuloma
Sinuses and fistula in the perianal
area, pyoderma gangrenosum, vasculitis,
aphthous ulcer
Melkersson-Rosenthal syndrome
Ref. Church, Int J colorect Dis, 8, 117, (1993)
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Q 20. A 42 yr old woman presents with a 3 yr
history of a persistent eruption with a butterfly
pattern on the face. She is otherwise well.
Examination of the lesion reveals scarring,
depigmentation, telangiectasia, follicular
plugging and carpet-tack scaling. There are no
other skin or mucosal abnormalities.

• What is the diagnosis?
• What are the main histological appearances of a
  skin biopsy?
• What are the approximate percentage chances of
  development of systemic involvement in this
  patient?
• What advice would you offer to prevent further
  extension of this lesion?

Discoid lupus erythematosus
Basal cell vacuolation and liquifaction degenerati
on, dermal inflmmatory infiltrate, often
periappendigeal
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Sun exposure avoidance, and use of sun screen
Ref. Southeimer, Lupus, 6, 84, (1997)