Drug Eruptions/Skin Drug Eruptions/Skin Emergencies/Signs of Emergencies/Signs of

Systemic DiseaseSystemic DiseaseDr Nagla KonborDr Nagla Konbor

University Hospitals Coventry and University Hospitals Coventry and Warwickshire NHS TrustWarwickshire NHS Trust

ObjectivesObjectives

Drug eruptions Drug eruptions

Skin emergencySkin emergency

Skin signs of internal malignancy Skin signs of internal malignancy

Skin signs of internal disease Skin signs of internal disease other than malignancy other than malignancy

UrticariaUrticaria

A flesh-coloured to pink, well circumscribed plaque caused A flesh-coloured to pink, well circumscribed plaque caused by dermal oedemaby dermal oedema

Itchy! Itchy!

Individual lesions last only a few hours, usually resolved Individual lesions last only a few hours, usually resolved within 24 hours within 24 hours

When caused by drugs, may be IgE mediated, triggering When caused by drugs, may be IgE mediated, triggering mast cell granule release; or drug may directly cause mast mast cell granule release; or drug may directly cause mast cell granule release cell granule release

Exanthem/Morbilliform Eruption Exanthem/Morbilliform Eruption

““Morbilliform" refers to a resemblance to the Morbilliform" refers to a resemblance to the rash of measles (morbilli is Latin for rash of measles (morbilli is Latin for measles)measles)

Symmetrically distributed on the trunk and Symmetrically distributed on the trunk and proximal extremities, and consists of bright proximal extremities, and consists of bright pink macules and slightly raised papules pink macules and slightly raised papules ("maculopapular") ("maculopapular")

Fixed drug eruption Fixed drug eruption

““Fixed" in that it occurs at same sites with Fixed" in that it occurs at same sites with each episode each episode

OTC drugs containing phenolphthalein, OTC drugs containing phenolphthalein, pseudoephedrine, etc. common culprits pseudoephedrine, etc. common culprits

Tetracyclines, barbiturates, phenothiazines, Tetracyclines, barbiturates, phenothiazines, sulfonamides sulfonamides

Oval, itchy or burning dusky red plaque Oval, itchy or burning dusky red plaque

Erythema Multiforme Erythema Multiforme

Range of illness from EM minor to EM major/Steven-Range of illness from EM minor to EM major/Steven-Johnson Syndrome to Toxic Epidermal NecrolysisJohnson Syndrome to Toxic Epidermal Necrolysis

Cell-mediated immune reaction, vasculitisCell-mediated immune reaction, vasculitis Rash range from iris/target lesion, to erythematous Rash range from iris/target lesion, to erythematous

maculopapular rash, urticaria, and vesicobullousmaculopapular rash, urticaria, and vesicobullous Dorsum of hands and feet and extensor surfaces Dorsum of hands and feet and extensor surfaces

EM MinorEM Minor

Acute self-limited eruptionAcute self-limited eruption Many causesMany causes

– medications (anticonvulsants, sulfa drugs, medications (anticonvulsants, sulfa drugs, chemo agents, NSAID’s)chemo agents, NSAID’s)

– infectious (Mycoplasma, Herpes)infectious (Mycoplasma, Herpes)

Limited mucosal involvement and limit organ Limited mucosal involvement and limit organ involvementinvolvement

Steven-Johnson SyndromeSteven-Johnson Syndrome

EM majorEM major < 10% body surface area< 10% body surface area More severe with more mucosal involvement than More severe with more mucosal involvement than

EM minorEM minor 5-15% mortality5-15% mortality Treatment: treat underlying cause (stop Treatment: treat underlying cause (stop

offending medication, valacyclovir), offending medication, valacyclovir), immunosuppression (cyclophosamide, immunosuppression (cyclophosamide, prednisone, cyclosporin), usually supportive care. prednisone, cyclosporin), usually supportive care.

Toxic Epidermal Necrolysis (TEN) Toxic Epidermal Necrolysis (TEN)

TEN is a medical emergency!TEN is a medical emergency! > 30% body surface area> 30% body surface area May represent severe form of SJSMay represent severe form of SJS Up to 70% mortality rateUp to 70% mortality rate Generalized epidermal sloughing with mucosal Generalized epidermal sloughing with mucosal

involvementinvolvement Warm tender erythroderma, vesicles/bulla Warm tender erythroderma, vesicles/bulla

exfoliationexfoliation + Nikolsky sign+ Nikolsky sign

Hemorrhagic crusting of the lipsHemorrhagic crusting of the lips Conjunctivitis commonConjunctivitis common Medications induced, infectious, or Medications induced, infectious, or

idiopathicidiopathic Treatment: supportive, removing offending Treatment: supportive, removing offending

agents, antibiotics for signs of infection, pain agents, antibiotics for signs of infection, pain controlcontrol

Staphylococcal Scalded Skin Staphylococcal Scalded Skin Syndrome (SSSS)Syndrome (SSSS)

Lyell’s diseaseLyell’s disease Caused by epidermolytic exotoxin from a group Caused by epidermolytic exotoxin from a group

2 staphylococcus (phage-type 71)2 staphylococcus (phage-type 71) Toxic, crying, pyrexialToxic, crying, pyrexial Burning of skin which is tender to touchBurning of skin which is tender to touch Widespread desquamation of the epidermis, Widespread desquamation of the epidermis,

periorbital, perioral and flexuralperiorbital, perioral and flexural Early recognition and systemic antibiotic can be Early recognition and systemic antibiotic can be

life-savinglife-saving

MeningoccemiaMeningoccemia

Neisseria meningitidisNeisseria meningitidis Seasonal prevalence (winter and early Seasonal prevalence (winter and early

spring)spring) Early symptoms – fever, petechial rash, Early symptoms – fever, petechial rash,

irritabilityirritability Later symptoms – lethargy, shock, DIC, Later symptoms – lethargy, shock, DIC,

purpura, thrombosispurpura, thrombosis Treatment – antibiotic and corticosteroid (if Treatment – antibiotic and corticosteroid (if

in shock and diagnosed early)in shock and diagnosed early)

Necrotizing FasciitisNecrotizing Fasciitis

Polymicrobial infection - spreads along Polymicrobial infection - spreads along superficial and deep fascial planessuperficial and deep fascial planes

Causes vascular occlusion, ischemia, and Causes vascular occlusion, ischemia, and tissue necrosistissue necrosis

Mortality up to 25%Mortality up to 25% Prodrome of fever and chills, followed by Prodrome of fever and chills, followed by

erythroderma and a vesicobullous rasherythroderma and a vesicobullous rash Treatment – Abx, surgical debridementTreatment – Abx, surgical debridement

Heparin induced necrosisHeparin induced necrosis

Coumarin NecrosisCoumarin Necrosis

Skin Signs of Internal MalignancySkin Signs of Internal Malignancy

Cutaneous metastases Cutaneous metastases

Paraneoplastic syndromes Paraneoplastic syndromes

Heritable "cancer syndromes" Heritable "cancer syndromes"

Sister Mary Joseph nodule Sister Mary Joseph nodule

Umbilical metastasis; poor prognosis Umbilical metastasis; poor prognosis Precedes or follows diagnosis of CA Precedes or follows diagnosis of CA CA sites (decreasing order of frequency): CA sites (decreasing order of frequency):

colon, ovary, pancreas, endometrium, colon, ovary, pancreas, endometrium, breast, small bowel breast, small bowel

Paraneoplastic SyndromesParaneoplastic Syndromes

The skin often presents a clue that an The skin often presents a clue that an internal malignancy is present. internal malignancy is present.

The combination of a malignancy and The combination of a malignancy and associated signs and symptoms that are associated signs and symptoms that are seemingly unrelated to the actual tumour is seemingly unrelated to the actual tumour is called a "paraneoplastic" syndrome. called a "paraneoplastic" syndrome.    

Erythema Gyratum Repens Erythema Gyratum Repens

““Wood-grain" pattern Wood-grain" pattern Wavy, erythematous, urticarial bands with Wavy, erythematous, urticarial bands with

scale scale Slowly migrate Slowly migrate Breast, stomach, bladder, prostate, cervix; Breast, stomach, bladder, prostate, cervix;

occasionally no CA occasionally no CA

Necrolytic Migratory Erythema Necrolytic Migratory Erythema

GlucagonomaGlucagonoma Occasionally no neoplasm found Occasionally no neoplasm found Abdomen, thighs and buttocks Abdomen, thighs and buttocks Patchy erythema with flaccid vesicles and Patchy erythema with flaccid vesicles and

bullae bullae Glossitis, angular cheilitis, normocytic Glossitis, angular cheilitis, normocytic

anemia, low amino acid levels in serum anemia, low amino acid levels in serum

Heritable “Cancer Syndromes"Heritable “Cancer Syndromes"

Peutz-Jehger syndrome Peutz-Jehger syndrome

Multiple hamartomatous polyps in small Multiple hamartomatous polyps in small bowel (most common), stomach and colon; bowel (most common), stomach and colon; low risk of bowel malignancy low risk of bowel malignancy

Multiple lentigines (freckle-like) of lips, nose, Multiple lentigines (freckle-like) of lips, nose, oral mucosa, fingertips and nail beds oral mucosa, fingertips and nail beds

Non-intestinal malignanciesNon-intestinal malignancies increased: increased: lung, lung, ovary, endometrium pancreas, myeloma ovary, endometrium pancreas, myeloma

Skin signs of internal disease Skin signs of internal disease other than malignanciesother than malignancies

Necrobiosis LipoidicaNecrobiosis Lipoidica

Well-circumsribed, firm, depressed, waxy, Well-circumsribed, firm, depressed, waxy, yellow-brown, lesions on the skin yellow-brown, lesions on the skin

Usually on the shin. 85% on the legsUsually on the shin. 85% on the legs 60% of NL has diabetes mellitus60% of NL has diabetes mellitus 20% of NL has impaired glucose tolerance 20% of NL has impaired glucose tolerance

or a family history of diabetesor a family history of diabetes Treatment: triamcinolone injection etcTreatment: triamcinolone injection etc

Pyoderma Gangrenosum Pyoderma Gangrenosum

Characteristic rapidly expanding ulcer with bluish Characteristic rapidly expanding ulcer with bluish undermined border; often lower extremities; begin as sterile undermined border; often lower extremities; begin as sterile pustules pustules

50% no disease association 50% no disease association 1% to 10% of patients with active ulcerative colitis; often 1% to 10% of patients with active ulcerative colitis; often

(but not always) parallels disease (but not always) parallels disease Other disease associations: Crohn’s, chronic active Other disease associations: Crohn’s, chronic active

hepatitis, rheumatoid arthritis, HIV infection; acute and hepatitis, rheumatoid arthritis, HIV infection; acute and chronic granulocytic leukemia (bullous PG) chronic granulocytic leukemia (bullous PG)

Can be associated with underlying malignancy (leukemia, Can be associated with underlying malignancy (leukemia, etc.) etc.)

XanthomasXanthomas

May be a sign of systemic metabolic abnormality May be a sign of systemic metabolic abnormality or a local cellular dysfunction or a local cellular dysfunction

Xanthomas may be the first sign of one the Xanthomas may be the first sign of one the hyperlipoproteinemias, rare but serious metabolic hyperlipoproteinemias, rare but serious metabolic diseases diseases

Xanthelasma are xanthomas of eyelids that may Xanthelasma are xanthomas of eyelids that may or may not be associated with hyperlipidemiaor may not be associated with hyperlipidemia

Eruptive xanthomas, tendon xanthomas, and Eruptive xanthomas, tendon xanthomas, and tuberous xanthomas are signs of significant tuberous xanthomas are signs of significant hyperlipidemia; these patients require careful hyperlipidemia; these patients require careful evaluation and prompt treatment evaluation and prompt treatment

Acanthosis Nigricans Acanthosis Nigricans

Velvety thickening and darkening (hyperpigmentation) Velvety thickening and darkening (hyperpigmentation) of the skin, especially on the nape of the neck, axillae of the skin, especially on the nape of the neck, axillae and other body folds and other body folds

Underlying causes may be hereditary or acquired, Underlying causes may be hereditary or acquired, and include:and include:– obesity; drugs; "malignant" acanthosis nigricans; hereditary, benign ANobesity; drugs; "malignant" acanthosis nigricans; hereditary, benign AN

Hyperinsulinemia is a common denominator Hyperinsulinemia is a common denominator

Erythema NodosumErythema Nodosum

Deep erythematous painful nodules, symmetrically Deep erythematous painful nodules, symmetrically on the lower legs; female predominance; a on the lower legs; female predominance; a hypersensitivity panniculitis hypersensitivity panniculitis

Fever, chills, malaise, leukocytosis Fever, chills, malaise, leukocytosis

Disease associations: streptococcal infections, Disease associations: streptococcal infections, drugs (OCPs, sulfonamides, iodides), pregnancy, drugs (OCPs, sulfonamides, iodides), pregnancy, TB, deep mycoses, acute sarcoidosis, inflammatory TB, deep mycoses, acute sarcoidosis, inflammatory bowel disease bowel disease

Telogen Effluvium Telogen Effluvium

A distinctive form of hair loss that is a response to A distinctive form of hair loss that is a response to an underlying systemic condition an underlying systemic condition

Normally, about 50-100 telogen hairs are shed Normally, about 50-100 telogen hairs are shed from the scalp each day; in telogen effluvium, this from the scalp each day; in telogen effluvium, this number is greatly increased number is greatly increased

The telogen hairs start falling out about 3 months The telogen hairs start falling out about 3 months after a "precipitating event--" major surgery, after a "precipitating event--" major surgery, severe illness, certain drugs, and childbirth being severe illness, certain drugs, and childbirth being the most common. Chronic disease or drug the most common. Chronic disease or drug ingestion can cause a sustained telogen ingestion can cause a sustained telogen effluvium--e.g., hypothyroidism, retinoid use effluvium--e.g., hypothyroidism, retinoid use

Erythema Chronicum Migrans Erythema Chronicum Migrans

Often the first manifestation of Lyme disease Often the first manifestation of Lyme disease Spirochete Borrelia burgdorferi is transmitted by the bite of Spirochete Borrelia burgdorferi is transmitted by the bite of

the deer tick Ixodes scapularis in the northeastern U.S. the deer tick Ixodes scapularis in the northeastern U.S. (other species elsewhere) (other species elsewhere)

Systemic borreliosis is a potentially serious disease, Systemic borreliosis is a potentially serious disease, causing both acute and chronic symptoms such as fever, causing both acute and chronic symptoms such as fever, malaise, arthralgia, carditis, arthritis, meningitis, etc.malaise, arthralgia, carditis, arthritis, meningitis, etc.

Typical lesion is a macule or papule that expands over Typical lesion is a macule or papule that expands over several days, with central clearing, to form an annular, several days, with central clearing, to form an annular, erythematous patch or plaque; may reach 15 or more CM erythematous patch or plaque; may reach 15 or more CM in size in size

Soldiers and Marines hiking through fields in endemic Soldiers and Marines hiking through fields in endemic areas are prone to this disease areas are prone to this disease

Leukocytoclastic Vasculitis Leukocytoclastic Vasculitis

““Palpable purpura," small, raised areas of Palpable purpura," small, raised areas of cutaneous hemorrhage and inflammation at the cutaneous hemorrhage and inflammation at the site of venular destruction site of venular destruction

May be associated with fever, joint pain, and May be associated with fever, joint pain, and internal organ damage (kidneys, GI tract, brain) internal organ damage (kidneys, GI tract, brain)

Lesions are usually numerous and tend to Lesions are usually numerous and tend to affect the legs and ankles most severely  affect the legs and ankles most severely 

Causes Causes Drugs, such as sulfonamides, penicillins, others Drugs, such as sulfonamides, penicillins, others Infections, such as Group A streptococcal, viral Infections, such as Group A streptococcal, viral

hepatitis (e.g. Hep. C), others hepatitis (e.g. Hep. C), others Immunologic diseases such as systemic lupus Immunologic diseases such as systemic lupus

erythematosus, rheumatoid arthritis, erythematosus, rheumatoid arthritis, cryoglobulinemia cryoglobulinemia

Neoplasms such as lymphomas Neoplasms such as lymphomas

Idiopathic--no cause found in @50% of casesIdiopathic--no cause found in @50% of cases

Thank YouThank You

Any questions?Any questions?