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Drug Eruptions/Skin Emergencies/Signs of Systemic Disease Dr Nagla Konbor University Hospitals Coventry and Warwickshire NHS Trust Objectives Drug eruptions Skin emergency Skin signs of internal malignancy Skin signs of internal disease other than malignancy Urticaria A flesh-coloured to pink, well circumscribed plaque caused by dermal oedema Itchy! Individual lesions last only a few hours, usually resolved within 24 hours When caused by drugs, may be IgE mediated, triggering mast cell granule release; or drug may directly cause mast cell granule release Exanthem/Morbilliform Eruption “Morbilliform" refers to a resemblance to the rash of measles (morbilli is Latin for measles) Symmetrically distributed on the trunk and proximal extremities, and consists of bright pink macules and slightly raised papules ("maculopapular") Fixed drug eruption “Fixed" in that it occurs at same sites with each episode OTC drugs containing phenolphthalein, pseudoephedrine, etc. common culprits Tetracyclines, barbiturates, phenothiazines, sulfonamides Oval, itchy or burning dusky red plaque Erythema Multiforme Range of illness from EM minor to EM major/StevenJohnson Syndrome to Toxic Epidermal Necrolysis Cell-mediated immune reaction, vasculitis Rash range from iris/target lesion, to erythematous maculopapular rash, urticaria, and vesicobullous Dorsum of hands and feet and extensor surfaces EM Minor Acute self-limited eruption Many causes – medications (anticonvulsants, sulfa drugs, chemo agents, NSAID’s) – infectious (Mycoplasma, Herpes) Limited mucosal involvement and limit organ involvement Steven-Johnson Syndrome EM major < 10% body surface area More severe with more mucosal involvement than EM minor 5-15% mortality Treatment: treat underlying cause (stop offending medication, valacyclovir), immunosuppression (cyclophosamide, prednisone, cyclosporin), usually supportive Toxic Epidermal Necrolysis (TEN) TEN is a medical emergency! > 30% body surface area May represent severe form of SJS Up to 70% mortality rate Generalized epidermal sloughing with mucosal involvement Warm tender erythroderma, vesicles/bulla exfoliation + Nikolsky sign Hemorrhagic crusting of the lips Conjunctivitis common Medications induced, infectious, or idiopathic Treatment: supportive, removing offending agents, antibiotics for signs of infection, pain control Staphylococcal Scalded Skin Syndrome (SSSS) Lyell’s disease Caused by epidermolytic exotoxin from a group 2 staphylococcus (phage-type 71) Toxic, crying, pyrexial Burning of skin which is tender to touch Widespread desquamation of the epidermis, periorbital, perioral and flexural Early recognition and systemic antibiotic can be life-saving Meningoccemia Neisseria meningitidis Seasonal prevalence (winter and early spring) Early symptoms – fever, petechial rash, irritability Later symptoms – lethargy, shock, DIC, purpura, thrombosis Treatment – antibiotic and corticosteroid (if in shock and diagnosed early) Necrotizing Fasciitis Polymicrobial infection - spreads along superficial and deep fascial planes Causes vascular occlusion, ischemia, and tissue necrosis Mortality up to 25% Prodrome of fever and chills, followed by erythroderma and a vesicobullous rash Treatment – Abx, surgical debridement Heparin induced necrosis Coumarin Necrosis Skin Signs of Internal Malignancy Cutaneous metastases Paraneoplastic syndromes Heritable "cancer syndromes" Sister Mary Joseph nodule Umbilical metastasis; poor prognosis Precedes or follows diagnosis of CA CA sites (decreasing order of frequency): colon, ovary, pancreas, endometrium, breast, small bowel Paraneoplastic Syndromes The skin often presents a clue that an internal malignancy is present. The combination of a malignancy and associated signs and symptoms that are seemingly unrelated to the actual tumour is called a "paraneoplastic" syndrome. Erythema Gyratum Repens “Wood-grain" pattern Wavy, erythematous, urticarial bands with scale Slowly migrate Breast, stomach, bladder, prostate, cervix; occasionally no CA Necrolytic Migratory Erythema Glucagonoma Occasionally no neoplasm found Abdomen, thighs and buttocks Patchy erythema with flaccid vesicles and bullae Glossitis, angular cheilitis, normocytic anemia, low amino acid levels in serum Heritable “Cancer Syndromes" Peutz-Jehger syndrome Multiple hamartomatous polyps in small bowel (most common), stomach and colon; low risk of bowel malignancy Multiple lentigines (freckle-like) of lips, nose, oral mucosa, fingertips and nail beds Non-intestinal malignancies increased: lung, ovary, endometrium pancreas, myeloma Skin signs of internal disease other than malignancies Necrobiosis Lipoidica Well-circumsribed, firm, depressed, waxy, yellow-brown, lesions on the skin Usually on the shin. 85% on the legs 60% of NL has diabetes mellitus 20% of NL has impaired glucose tolerance or a family history of diabetes Treatment: triamcinolone injection etc Pyoderma Gangrenosum Characteristic rapidly expanding ulcer with bluish undermined border; often lower extremities; begin as sterile pustules 50% no disease association 1% to 10% of patients with active ulcerative colitis; often (but not always) parallels disease Other disease associations: Crohn’s, chronic active hepatitis, rheumatoid arthritis, HIV infection; acute and chronic granulocytic leukemia (bullous PG) Can be associated with underlying malignancy (leukemia, etc.) Xanthomas May be a sign of systemic metabolic abnormality or a local cellular dysfunction Xanthomas may be the first sign of one the hyperlipoproteinemias, rare but serious metabolic diseases Xanthelasma are xanthomas of eyelids that may or may not be associated with hyperlipidemia Eruptive xanthomas, tendon xanthomas, and tuberous xanthomas are signs of significant hyperlipidemia; these patients require careful evaluation and prompt treatment Acanthosis Nigricans Velvety thickening and darkening (hyperpigmentation) of the skin, especially on the nape of the neck, axillae and other body folds Underlying causes may be hereditary or acquired, and include: – obesity; drugs; "malignant" acanthosis nigricans; hereditary, benign AN Hyperinsulinemia is a common denominator Erythema Nodosum Deep erythematous painful nodules, symmetrically on the lower legs; female predominance; a hypersensitivity panniculitis Fever, chills, malaise, leukocytosis Disease associations: streptococcal infections, drugs (OCPs, sulfonamides, iodides), pregnancy, TB, deep mycoses, acute sarcoidosis, inflammatory bowel disease Telogen Effluvium A distinctive form of hair loss that is a response to an underlying systemic condition Normally, about 50-100 telogen hairs are shed from the scalp each day; in telogen effluvium, this number is greatly increased The telogen hairs start falling out about 3 months after a "precipitating event--" major surgery, severe illness, certain drugs, and childbirth being the most common. Chronic disease or drug ingestion can cause a sustained telogen effluvium-e.g., hypothyroidism, retinoid use Erythema Chronicum Migrans Often the first manifestation of Lyme disease Spirochete Borrelia burgdorferi is transmitted by the bite of the deer tick Ixodes scapularis in the northeastern U.S. (other species elsewhere) Systemic borreliosis is a potentially serious disease, causing both acute and chronic symptoms such as fever, malaise, arthralgia, carditis, arthritis, meningitis, etc. Typical lesion is a macule or papule that expands over several days, with central clearing, to form an annular, erythematous patch or plaque; may reach 15 or more CM in size Soldiers and Marines hiking through fields in endemic areas are prone to this disease Leukocytoclastic Vasculitis “Palpable purpura," small, raised areas of cutaneous hemorrhage and inflammation at the site of venular destruction May be associated with fever, joint pain, and internal organ damage (kidneys, GI tract, brain) Lesions are usually numerous and tend to affect the legs and ankles most severely Causes Drugs, such as sulfonamides, penicillins, others Infections, such as Group A streptococcal, viral hepatitis (e.g. Hep. C), others Immunologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, cryoglobulinemia Neoplasms such as lymphomas Idiopathic--no cause found in @50% of cases Thank You Any questions?