The Flushing Patient
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Transcript of The Flushing Patient
The flushing patient: Differential diagnosis, worku
p, and treatmentJ Am Acad Dermatol 2006;55:193-208
Introduction
• Cutaneous flushing– Resulting from changes in cutaneous blood fl
ow triggered by multiple conditions– Common, benign diseases, such as rosacea o
r climacterum– Other serious diagnoses; carcinoid syndrome,
pheochromocytoma, mastocytosis, and anaphylaxis
Definition
• Defined as a sensation of warmth accompanied by visible reddening of the skin.
• Usu. Most prominent in the classis “bluish area,” including the face, neck and upper portion of the chest, and upper limbs
Definition II
• Flushing – episodic or constant
• Episodic attacks are generally mediated by release of endogenous vasoactive mediators or by drugs
• Repetitive episodes over long periods (persistent flushing)
• May produce fixed facial erythema with telangiectases and a cyanotic tinge
Differential Diagnosis
Fever
• Most common cause of “hot flushes”, associated with night sweats
• Prompt a fever workup, which may reveal an infectious or noninfectious cause
Benign Cutaneous Flushing
• Triggered by emotion, exercise, temperature changes, and foods or beverages, esp. spicy foods
• Associated findings – a feeling of warmth and cognitive dysfunction
• Hyperthermia, Emotional flushing, Foods, beverages, and alcohol
Rosacea
• Acne rosacea- another common cause
• May present with transient or persistent central facial flushing, erythmea, visible blood vessels, and often papules and pustules
• 4 broad subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular
Rosacea
Rosacea II
• Primary manifestation– Persistent erythema, usu. Longer than 3 mont
hs– Flushing episodes, lasting longer than 10 min
s
• Important to exclude polycythemia vera, connective tissue disease, carcinoid syndrome, systemic mastocytosis
Climacteric Flushing
• Common cause of flushing, affecting 50%~85% of women who undergo natural menopause
• Perimenopausal flushing presents as transient episodes of intense heat sensation, flushing of the chest, head, and neck, and profuse drenching sweats
• Frequently followed by chills, palpitations and a sense of anxiety
• Episodes last 3-5 mins and may occur as many as 20 times a day
Carcinoid Syndrome
• Classical triad: flushing, GI hypermotility and Rt sided cardiac failure. Lesser incidence of bronchoconstriction
• 95% of p’ts have flushing at some point during disease; the most frequent sign
• CS occurs in 10% of p’ts with carcinoid tumors; malignant enterochromaffin or Kulchitsky cells derived from neuroendocrine lineage
• 13% had metastasis at time of diagnosis and 24% carcinoid p’ts had more than 1 tumor
Carcinoid Syndrome II
• Flushes ossicated with gastric tumors are reddish-brown with variegated margination and occurs as wheals over the entire body, including palms and soles and intensely pruritic
• Flushes assoicated with bronchoconstriction are bright red and confluent, cover most of the body, last hours to days, and usu. Associated with chemosis, facial edema, severe hypotension, and oliguria
• P’ts with CS flushing may develop thick skin changes with venous telangiectasia and bluish coloration of the chin, nose and malar area
Carcinoid Syndrome III
• P’ts generally presents with hypotension and tachycardia during flushing
• Flushing may be provoked by foods, pharmalocologic triggers and any stimuli that increase adrenergic activity
• Likelihood of flushing in CS is dependent on tumor-derived mediators and the extent of liver metastasis
Carcinoid Syndrome IV
• Tumor derived vasodilator : 5-HT, substance P, histamine, serotonin, catecholamines, PG, kallikrein, kinins, tachykinins, neuropeptide P, VIP, motilin, and gastric related peptides
• CS diagnosed by measuring 24-hr urine 5-HIAA, a major urinary metabolite of 5-HT
• Flushing in CS can be blocked with somatostatin, analogs also decrease tumor progression
Pheochromocytoma
• Also known as chromaffin tumor, present with flushing and hypertension
• Chromaffin cells derived most often from the adrenal medulla, produce, store and release catecholamines
• HTN most common finding.• Attacks last a few minutes to a few hours• Associated with flushing or pallor, elevated BP a
nd tachycardia• Commonly present with headaches, sweating, p
alpitations, a sense of apprehension and impending doom, chest or abd pain.
Pheochromocytoma II
• Diagnosed by 24hr urine fractionated metanephrines, metabolites of catecholamines
• Abdominal CT, abdominal aortography or nuclear scintigraphy with radioactive iodine
• Surgical resection by laparoscopic adrenalectomy is the definitive treatment and may be curative
Mastocytosis
• A rare disease caused by tissue infiltration with increased numbers of mast cells
• More common in childhood than in adulthood
• Presents in the children with the characteristic skin eruption of urticaria pigmentosa (>90%)
Urticaria pigmentosa
Darier sign
• Darier sign is a change observed after stroking the skin of a person with systemic mastocytosis or urticaria pigmentosa. In general, the skin becomes swollen, itchy and red.
• Result of stimulation; mast cells release several potent vasodilators; histamine and PG D2, TNF α
Mastocytosis II
• Diagnosis usu. straightforward if characteristic lesions of urticaria pigmentosa present
• Elevated plasma concentrations of mast cell mediators, such as histamine and tryptase
• Elevated 24hr urine excretion of histamine and PG D2
• Histopathologic analysis of cutaneous mastocytosis lesions revealing multifocal or diffuse mast cell aggregates
Mastocytosis III
• Classified into 4 categoriesI. Indolent mastocytosis, cutaneous or syste
mic
II. Mastocytosis associated with hematologic disease
III. Lymphadenopathic mastocytosis with eosinophilia
IV. Mast cell leukemia
Mastocytosis IV
• No cure for mastocytosis
• Avoidance of precipitating factors
• Flushing and hypotension from mastocytosis can be reversed with IV epinephrine
• Combined blockade pf H1 and H2 receptors prevents the vasodilatory effects of histamine
Anaphylaxis
• Life threatening condition that may present with flushing
• Most often presents with flushing, urticaria and angioedema
• Hypotension, upper airway edema, pulmonary symptoms, rhinitis, headaches and substernal chest pain
Medullary Ca. of the thyroid
• Malignant tumor of the parafollicular C cells
• May present with protracted flushing of the face and upper extremities, discoloration, and telangiectasias
• Neoplastic cells are derived from neural crest
• Inheritance pattern may be sporadic or AD
Pancreatic cell tumor
• Vasoactive intestinal polypeptide (VIP) tumor classically present with Verner-Morrison syndrome: watery diarrhea, hypokalemia, and achlorhydria
• Also rarely present with flushing during attacks
• VIP tumor is diagnosed by a high plasma VIP level in the setting of stool volume greater than 1L per day
Renal cell carcinoma
• RCC may cause flushing via secretion of prostaglandin or via pituitary downregulation from release of gonatotropins
• Classic triad: gross hematuria, flank pain and abdominal mass
• Tx of choice: Nephrectomy
Pharmacologic mediators
Pharmacologic mediators
Differential Diagnosis
Unilateral flushing
• May result from contralateral sympathetic nerve lesions that produce Horner syndrome (ptosis, miosis, and anhidrosis)
• Leading to contralateral, unaffected facial reddening
Medications
Summary
Summary