The Skin in Systemic Diseases

1. 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

2. 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; sacriliac’spinal; arthritis mutilans* Pitting; onycholysis HIV *ref. Moll & Wright, Semin. Arthr. Rheum. 3, 55, (1973)

3. 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 AL amyloidosis • 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? 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

4. 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 Dermatomyositis • 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? Gottron,s papules Serum creatininie kinase Muscle biopsy for histology Serum creatinase Internal malignant neoplasia (Paraneoplastic syndrome)* *ref. Callen, Lancet, 357, 85, (2001)

5. 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. Reiter’s syndrome • 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? Chlamydia sp. Keratoderma blenorrhagicum HLA B27* *ref. Archer et al, Br J Rheumatol, 27,306,1988

6. 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 C’4 level (low value = positive screening test), serum C’1 inhibitor level (low value confirms diagnosis)* Dominant Fresh frozen plasma IV, C’1 inhibitor concentrate IV *ref. Agostoni, Medicine 71, 206 (1992)

7. 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 Henoch Schonlein purpura • 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?* -haemolytic streptococcal sore throat Kidneys, intestine IgA immune complex *ref Tancrede-Bohin et al, Arch Dermatol 133, 438, (1997)

8. 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)

9. 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)

10. 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))

11. 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)

12. 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 Pyoderma gangrenosum • 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? Ulcerative colitis or Crohn’s disease Rheumatoid arthritis, leukemia, paraproteinaemia, autoimmune connective tissue disease, Behcet’s syndrome* Corticosteroids Ref. Powell et al, Amer J Med, 55, 173, (1985)

13. Q 12. A 38 yr-old housewife, recovering from a recent stroke, presents with a 2-yr history of Raynaud`s 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 Sneddon’s syndrome* Anti-phospholipid antibodies Recurrent abortion *Ref. Sneddon, Br J Dermatol, 77, 180, (1965)

14. 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)

15. Q 14. This 28 yr old woman had multiple nodules and polypi on the trunk and limbs “since birth”and 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 son`s 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 phaechromocytoma, hypertension *Ref. Riccardi, NEJM 305, 1617, (1981)

16. 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)

17. 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 Tuberous sclerosis* • 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? 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)

18. Q 17. A 45 yr-old woman, previously treated for thyrotoxicosis, but now not on treatment, has developed dermal nodules on both lower legs Pretibial myxoedema • 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? Eye changes (proptosis, exophthalmos, lid retraction)* Dermal deposition of glycosaminoglycans No effect *Ref. Fatourechi et al, Medicine, 73, 1, (1994)

19. 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 patient`s 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)

20. 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? Crohn’s 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)

21. 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 degeneration, dermal inflmmatory infiltrate, often periappendigeal 5%* Sun exposure avoidance, and use of sun screen *Ref. Southeimer, Lupus, 6, 84, (1997)