‘well. Recommend patients to avoid aleohol-containing solutions tha flare the disease. Aluminum acetate solu tion can be used to maintain seborrheic otitis extema, Patients with sebortheic blepharitis can be treated ‘with warm to hot compresses and washing with baby shampoo followed by gentle cotton tip debridement of thick scale, Avoid ocular glucocorticoids. Ophthalmic sodium sulfacetamide ointment can be used for resis- tant seborrheic blepharitis ‘There are many other alternative treatments. Oral antifungals should be reserved for severe and refrac- tory eases due to potential drug interactions and side ‘effects. Allylamines may also be effective including topical butenafine and naltifine cream for mild cases versus oral terbinafine for extensive [Link]- jum succinate and lithium gluconate, both available in ‘some countries, have antifungal properties that ean be ‘used for treatment as well. Vitamin D3 analogs (cali- ppotriol cream or lotion) have both antiinflammatory and antifungal properties and can be used in selected patients as well. Other alternatives include topical ‘metronidazole eream or gel, once to twice daily. Oral isotretinoin in low doses (25-5 mg daily; or 0.1-03 mg/kg/day) over 3-5 months can be used in refrac- tory disease, of course while observing requirements in child-bearing females. Phototherapy with narrow- band ultraviolet B or psoralen plus ultraviolet A ean also be used in severe and refractory disease, but may be ineffective if patients have thick hair” Chapter 23 :: ACKNOWLEDGMENTS ‘We would like to thank Gerd Plewig and Thomas Jan- sen for their previous editions of this chapter on seb- ortheic dermatitis and the use of their format, tables, boxes, and photos while revising this chapter. KEY REFERENCES ull reference is available at www: [Link], DVD contains references and additional content 2 Johnson BA etal: Teatment of sebortheic deena. Am Fam Pls 61:2705-2714, 2000, 15, DeAngelis YM et ak Three eologic facets of dandraff and schortheie dermatitis Malasse7ia fangs, eebaccous lipids, and individual sensitivity J rest Dermal 10295287, ao7 48, Arora V ela: Management of infantile sebortheic derma- ‘Am Fam Pysc 73(6) 07,2007 453, Shin H et a Clinical efficacies of topical agents forthe treatment of sebortheic dermatite ofthe scalp: A compar ative study. j Dermatol 366) 131-137, 2008 56, Nowieki & Mederm management of dandruf, Pl Merkur Tears 20(115} 121-124, 2008 458, Bikowski J Facial sebortheie dermatitis: A report on cur- rent status and therapeutic horizons. Drugs Dermatol (2,125.13, 2008 467. Gupta AK etal: Biology and management of sebortheic dermatitis, Dermatology 208(2) 89-83, 2004 Exfoliative Dermatitis Jane Margaret Grant-Kels, Flavia Fedeles, & Marti J. Rothe em XEOLIATINE OEM ATS ATS GN * Exfoliative dermatitis (ED) is defined as diffuse erythema and sealing of the skin involving more than 90% of the total body skin surface area ' Systemic and potentially life-threatening complications include fluid and electrolyte imbalance, thermoregulatory disturbance, fever tachycardia, high-output failure, hhypoalbuminemis, and septicemia + Common underlying etiologies are psoriasis, atopic dermatitis, and other spengiotic dermatoses, drug hypersensitivity reactions, and cutaneous Tell lymphoma (CTCL) “The cause of ED is unknown (idiopathic) in approximately 20% of eases ' Diagnostic workup includes a complete history and physical examination, with careful analysis of pertinent clinical dues and dermatohistopathology. Other laboratory workup is often required and determined by clinical cues, 1 Management of ED involves combining symptomatic relief with addressing the ‘underlying etiology and potential systemic complications. Inpatient hospitalization is required in acute cases. = Prognosis is variable and depends primarily on the underlying etiology: Drug-induced ED has the best prognosis while malignancy-associated ED ‘has the highest mortality,EPIDEMIOLOGY Several lange studies have reported a widely varied incidence of exfoliative dermatitis (FD) ranging fom 9 to 71.0 per 100,000 ouspatients “A male predomi rrance has been described, with a male-to-female ratio of approximately 2:1 to 11, Any age group can be afected, and with most studies exluing children, the average age of disease onset varies from tI to 61. ED is, ‘rare disease in children, and only little epidemiologic data is available for pediatric populations. One study {ound 17 patients, recorded over a 6-year period, with ‘a mean age of onset of 3.3 years and a male-to-female ratio of 0.8911" ED oceurs inal races ‘A preexisting dermatosis plays a role in more than one-half ofthe cases of ED. Psoriasis isthe most com= zon underlying skin disease (almost one-fourth of the cases) In a recent study of severe psoriasis, ED was reported in 87 of 160 cases” ETIOLOGY AND PATHOGENESIS Establishing the etiology of ED can be challenging since it can be caused by a variety of cutaneous and systemic diseases (Table 23-1). A compilation of 18, published studies'*** from various countries on ED shows that 2 preexisting dermatosis is the most frequent cause in adults (52% of ED cases; range, 27ie68%) followed by drug hypersensitivity reac- tions (15%), and cutaneous T-cell lymphoma (CTCL) ‘or Sézary syndrome (5%). No underlying etiology is identified in approximately 20% of ED cases (range, 7%-33%4) and these cases are classified as idiopathic. Psoriasis is the most common underlying skin dis- cease to cause ED (23% of cases), followed by spongi- ‘otic dermatitis (20%). Possible triggers for psoriatic ED include the following: = Medications, such as lithium, terbinafine, and anti- malarials = Topical iritants including tars * Systemic illness * Discontinuation of potent topical or oral corticoste- roids, methotrexate, or biologics (efalizumab)™” * Infection including human immunodeficiency virus (HIV) = Pregnancy, = Emotional stress = Phototherapy burns Less common causes of ED in adults include immu- nobullous disease; connective tissue disease; infec tions, including scabies and dermatophytes; pityriasis, rubra plans (PRP) (1% of dermatoses); and underlying, ‘malignancy. Even in patients with underlying derma- tose itis citical to consider other possible etiologies. In one ease series, malignancy-related ED was identi- fied in seven patients, five of whom had a preexisting dermatosis." In about 5%-10% of idiopathic ED eases, cerythrodermic CTCL was ultimately diagnosed” Solid ‘organ malignancies as well as hematologic and reticu- loendothelial malignancies may manifest as ED. In neonates and infants, the differential diagnosis includes dermatoses (such as psoriasis, atopic derma- tits, and seboreheic dermatitis), drugs, and infection {particularly staphylococcal seaided-skin syndrome). Im addition, several congenital disorders includ- ing the ichthyoses, both bullous and nonbullous congenital ichthyosiform erythroderma, Netherton syndrome, and immunodeficiencies should be con- sidered (Box 23-1) “Topical and systemic medications are implicated ina significant percentage of ED cases (15%, range, 439%) and the introduction of new drugs islikely to increase the incidence of ED. Both allopathic and natu- ropathic medications have been suggested to cause ED and the list is constantly expanding (Table 252) "The most commonly implicated drugs include calcium channel blockers, antepileptics, antibiotics (penicillin family, sulfonamides, vancomycin), allopurinol, gold, lithium, quinidine, cimetidine, and dapsone. However, ‘most ofthe drugs are reported in single case reports. In addition to drugs, the contrast medium iod:xanol (Visipaque) used during percutaneous coronary inter ‘ventions has recently heen reported to cause ED ‘Currently, the pathogenic mechanisms of ED have not been elucidated. It is not well understood how a preexisting dermatosis progresses to ED, an under- Iying disease manifests a5 ED, or the de novo ED develops. While the clinical presentation is similar in patients with diverse etiologies of ED, iis likely that ifferent pathways lead to the common end result of skin-selectve recruitment of inflammatory cells ‘Cytokines, chemokines, and their receptors are believed to play an important role in the pathogen ‘sis of ED. A study of cytokine profile in dermal infiltrates showed that there may be differences in pathophysiologic mechanisms between benign ED and Sézary syndrome—a I helper 1 cytokine profile ‘was found in benign ED while 8 T helper 2 cytokine profile was found in Sézary syndzome." In a recent eport, an overexpression of both T helper 1- and helper 2-elated chemokine receptors (CCRS, CCRS, and CXCR3) was found in ED of inflammatory or fin, while a selective overexpression of CCRA was found in Sérary syndrome,” suggesting that Sézary syndrome is a T helper 2 disorder and that different pathways may contribute to skin homing of reactive Iymphocytes in different etiologies of ED. Another study showed that Sézary syndrome and inflamma tory ED are characterized by different memory T-cell subset expression further suggesting diferent patho- Physiologic mechanisms ‘The interaction between adhesion molecules and their ligands is important during inflammatory and ‘immunological responses. Increased circulating levels, ofadhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin) have been reported in benign reactive ED seconclary to proriasis and atopic dermatitis compared to controls.” Incontrast,no differences in expression levels ofthese molecules on endothelial cells were found in different types of ED, leading to the hypothesis that there are similarities in end-stage immunologie pathways in dif- ferent types of ED.” 267Dermatoses "= Spongiotie dermatitis Atopic dermatitis" *Seborheic sermatti? = Contact dermatitis Stasi dermatitis "Bullous = Pemphigus foliaceus” = Paraneoplastic pemphigus" Bullous pemphigoid 'Halley-Halley”” =Papulosquamous Pron” = Generalized ustular psoriasis” =Pryrass rubra pias "impetigo herpetiformis” =Photorentive = Chromatic serrate, sAetinicreticulid” Adverse drug? Acute generalized cexanthematous pustulosis ‘Toxic epidermal necalyss otner = Pseudo homa™ Erythema gyatum 1 Perorati felt 1 Radiation recall dermatitis! Senile erthr: cerma with ype ge ‘Most common deats. Systemic " Dermatomyost * Subacute cutane ‘ous lupus" heute grateversus- host disease™ " Posoperaive teansfusion induced” * Tryrotoicosi™ = Sarcoidosis"? * Hyperalitonemia”™ * éiopathic hype reosinophic syn ‘dome”™ + Monoclonal gam rmopathy of nde termined signifcance™ ‘+ Hemophagocytic histiogytoss vial sezocated”™” Infections Bacteral Tuberculosis Congenital sypilis” *Vial Hepatitis "Human immo: nodeticieney Human herpes virus 6" * Fungal "Dermat prsvise =Histoplasme: = Congenital cua candace Parasite " Nonesian ca bes" ‘Toxoplasmoss™ Leishmania " Tosin-mesisted infecsons Staphylococcal scalded-skin synarome™ ‘Tone shock syndrome Malignancy Sold mors Senge Prostate’? *Thyro* suena "caller * Melanoma” Breast™ Ovary" * Fallopian tube” * Esophagus" *Stomach™* Rectum’ Colon" Thymus jrchke-Loewenstein turer” Lymphoproliferive " Cotaneous Tl Iymphoms* 1 Sézarysynérome * Papuloerytroderms of fy "Hedin ymphoma'=*" "B-cell lymphoma * (Cutaneous anaplastic large calllymphoma"* " Angioimmunoblasti all lymphoma’ "Castleman disease * Acute myeloid leukemia Me" * Acute myelomenceytc leu hemia™ "Adah cal eukeria”? 1 Tell prolymphocytic! ‘ukemi + Chreniclymphooy levkema"™ + Chronic myelogencus teukema” * Chronic eosinophil leukema™ ' Nyelosyspasia™ * Premalignant myelopreliera- tive czorder™ + Multiple myeloma " Reticuli cell sarcoma? * Angioimmnoblasic lymphadenopathy" * Cutaneous imphoid hyperplasia * Hypereosinophit syn ee * Nastocytoss type ivy" "Hisocstose™| " Rosai-Dorfman disease Congenital " immunadetcency * Common varable hypo: sgammaglobulinema”™ "= Wiskott-Alerichsyncrome 1 Severe combined immu nodeicieney ‘Omen syncrome® Leiner disease "= HyperimmunoslobulinE (hyperigf syndrome” "secretory WA deficiency "Metabolic * Maple syrup urine disease ‘ Newval pid storage disease "Essential fatty ace def ciency ‘Propionic acidemia” *Hoocarboxylase synthe- tase deficiency” "esthyess "Bullous congentil ety: cosform erythroderma += Nonbullous congenital Ichthyostorm erytvederma 'sNetherton syndrome” "= Conradi-Hinermann synarome” "Epidermolytchyperkera Keratis fehthyoss and cexines:"™ Lamellar icthyosi "Lethal congenital erythro- dermna™ 1 5j5gren-Lasson syr- rome other ' Anigloblepharon- ectodermal eysplasicleting symarame AEC)"‘Most Likely = Spongiotic dermatitis (20%%-24%) (atopic, 9%; ‘contact dermatitis, 6%; sebortheic dermatitis, 496; chronic actinic dermatitis, 3%) Psoriasis (2356) Drug hypersensitivity reaction (1588) Cutaneous cell lymphoma (55) Idiopathic (approximately 20%) Consider = Contact dermatitis = Immunobullous disease (superficial pemphigus, bullous pemphigoid, paraneoplastic pemphigus) 1 Infection (scabies, dermatophytosis) “Toxin-mediated (toxic shock syndrome, staphylo «occal scalded-skin syndrome) Chronic actinic dermatitis = Pityriasis rubra plans * Collagen vascular disease * Paraneoplastic (solid tumors and hematologic) * Primary immunodeficiency = Congenital ichthyoses Always Rule Out = CutaneousT:cel lymphoma ' Drugrinduced hypersensitivity syndrome = Paraneoplastic ‘The complex interaction between adhesion mol ecules and cytokines likely contributes to the signifi cantly increased mitotic and epidermal turnover rate in ED. The scaling of ED skin isa reflection of decreased transit time through the epicermis and leads to sig- nificant loss of protein, amino acids, and nucleic acids Protein loss may increase by 25%-30% via scaling in psoriatic ED, and 10%.-15% innonpsoriatic ED.* Addi- tionally, protein-losing enteropathy may contribute to hypoalbumineria ‘Some patients with chronic idiopathic ED have been reported to develop CTCL that has led to con- cern that patients with chronic idiopathic ED may be at increased risk for progression to mycosis fungoides ‘or Sézary syndrome." The chronic Tell stimulation in these patients has been suggested to promote the development of CTCL" Recently, a premalignant ‘or pre‘Sézary-like condition has been described in elderly patients with chronic or relapsing ED without progression to hematologic malignancy characterized by a monoclonal expansion of CD#*CD7-CD26" lym- phocytes." The term monoclonal T-cell dyscrasia of ‘undetermined significance (MTUS),a'T-cell equivalent to monoclonal gammopathy of undetermined signifi cance, has been proposed for this condition, which is believed to be probably benign" However, chronic idiopathic ED may also represent primary. chronic, undiagnosed CTCL, Indeed, in up to 10% of idiopathic ED cases, erythrodermic CTCL is ultimately diag nosed. ‘A role for immunoglobulin (Ig) E in ED has been proposed based on the observation of increased IgE levels in many types of ED. For example, it has been theorized that elevations in IgE in psoriatic ED may point to a change from aT helper 1 cytokine profile in psoriasis to a T helper 2 cytokine in psoriatic ED." ‘This secondary mechanism is different than the pri- mary overproduction of IgE in atopic dermatitis Hyper-gE syndrome is an immune deficiency that has been associated with ED, and has high IgE production due to selective insufficient interferon-y secretion” ‘The mechanisms related to this elevation of IgE may be related to the underlying disease process or to the _manifestation ofthe disease as ED. Again, the mecha- nisms of IgE elevation appear to be different in differ- ent types of ED. Recently, it has been theorized that Staphylococcus aureus colonization or another antigen, such as toxic shock syndrome toxin-1, may play a role in the patho- {genesis of ED." Researchon theimmunopathogenesis ‘of toxin-mediated infection demonstrates staphylo- ‘coccal pathogenicity islands encoding superantigens (see Chapter 177). These islands carry the genes for the toxins of toxic shock syndrome and staphylococ- ‘al scalded-skin syndrome." 83% of patients with ED ‘were noted to have S. aureus colonization in the nares, ‘while 17% had colonization in the skin; however, oly ‘one in six patients was S. aureus enterotoxin positive.” (See Tables 23-1 and 23-2.) CLINICAL FINDINGS Figure 28-1 is an algorithm showing the approach to a patient with ED. HISTORY ‘A detailed history of a patient who presents with ED is an important tool for diagnosing the underlying eti- ‘ology. The patients may have a history of dermatoses (psoriasis, atopic dermatitis) or a systemic medical condition. A thorough medication history should be licited, including naturopathic and over the counter therapies. Patients with history of psoriasis and atopic dermatitis should be queried specifically regarding use of topical and systemic corticosteroids, metho" trexate, and other systemic medications; topical irri- tants; systemic illness; infection; phototherapy burns; pregnancy; and emotional stress. ED patients com- ‘monly report thermoregulatory disturbances, malaise, fatigue, and pruritus; these symptoms are not specific toany etiology: ‘The onset of symptoms is important to assess dif. ferent etiologies of ED. Primary skin diseases have 1 slower course while drug reactions usually have a rapid onset and resolution. One exception is ED asso- ciated with drug hypersensitivity reactions due to anticonvulsants, antibiotics, and allopurinol. This reac- tion develops in 2-5 weeks after medication is started 268A TABLE 23-2 Drugs implicated in Exfoliative Dermatitis* Anubioves ‘hareonam Cefonitin”™™ Deryeycine’” Gentamicin* bona Minoeycine Neomycin Ponce Ribostamycin® Rampin Streptomycin Sufasalarine™* Siafonamises"** “Teicopanin™ Thieetazone? ‘ebramycn"? Trimethoprim! Vancomycin"? Antiviral Dideoryinesne India Interferon 0" Zidovudine”? Anepromatous Clofszimine™ | Sein Anifungals Nystatin Terbinafine Ketoconazole" Geseofulin™” Arwiepleptcs Cobanazepine’33 Lamotrigine! Prenton Phenobarbca* Azreonam “atest commonly implicated drugs ar in ais. Antinfiammatory Aspirin Celecoxib Diftnisal® Metamzole™ Phenylbutazone? Prroxcam"® cardiac dtugs ‘Amiodarone Captopri Ditazern"* Enalapril eovobide dintrate” Mesletine Nifedipine” Natrosiyeern™ Practool Quinine” Verapamil ‘chematherapy Bevacizumaa” Carboplatin” Cisplatin” Denileukinettox”™ Dexorubicin™ Forourac Imatii™ itorycin Pentoctatin Vinca alaloids™ Diabet ‘Sulfonyureas Chlorpropamide* Psychiatrie Barbas Bupropion”? Chlorpromazine! Desipramine! Escala’ Etumine™ Fluoxetine Imipramine? Liu Phenethazines Methyiphenidate* Aspirin ‘and may remain ongoing after discontinuation of the ‘medication. Associated signs of a possible drug etiol- ‘ogy include fever, lymphadenopathy, organomegaly, ‘edema, leukocytosis with eosinophilia, and liver and renal dysfunction. History and clinical presentation alone may not be sufiient to diagnose ED dus to internal malignancy. Important clues for this diagnosis are an absence of prior skin disease, gradual ontet and alackof response fo standard therapies. history of transplant should 270 raise suspicion of CTCL, asithas been found that there other ‘Aopurinol" ‘prema sence BaclleCalmett-Guérn immunization"™* Bromedeoxyuridine™ Gimetidine™ | Clocronste"* Coane Efatzumab'™ Ephedrine! Epoprestenot™ Erythropoietin Ethyenediamine™” Fluncione™ Furosemide eos Homeopathic medline (NatMtu200)"* Hypericum ([Link] wert) Interleukin 27" lodine™ Lefunomide’” Mercurial Omeprazole'™™ Phenolphthalen"* Propolis Pseudoephedrine Raniiine™ Retinoigs?™=" Rhus dacques)™* Roxatdine acetate hyerochivide™ Terbutaline” ‘evachloroethylene! ‘Taldomide™” Thiasde!™ Timolel eye drops Teallzumab™ Tramacel Tumor necrosis factor Valyanaryana" Allopurinol™" isa higher frequency of ED secondary to CTCL in post- ‘ransplant patients.” tines ‘The classic presentation of ED is erythematous patches that increase in size and coalesce into generalized red ‘erythema with a shiny appearance. By definition, ED involves more than 90% of the patient’s skin surface (Fig. 23-2). A few days after the onset of erythema, fine‘Approach to patient with exfoliative Look for clues to Pero mate (Consider accion Leg. { Refer to POP torte ology on punchDiopsios; (QA) “tests such as: P| ut systemic cisease history and physical consider mutiple biopsies for drect ‘examination repeat biopsies in 3-6 Immunotuorescone ‘months for increased ‘gene rearrangement, ‘agnostic yiels Bc, CoA: COB rato, (CXR, lymph nede Figure 23-1 Approach to patient wi PCP = primary care physician, white or yellow scaling begins, classically arising in the flexures. Plate-like scaling may oceur acutely and con the palms and soles, The scaling progresses further, giving the skin a dull red appearance. With chronic- ity, edema and lichenification lead to skin induration, Ectropion and epiphora may develop secondary to chronic periorbital involvement (Fig. 23-3). Palmo- plantar keratoderma (Fig. 23-4) has been noted in up to 80% of patients with chronic ED." Figure 23-2 Ffliative dermattisin psoriasis Theres un versal erythema, thickening ofthe skin, and heavy sealing ‘The patient had fatigue, malaise, and vas shivering, biopsy xfoliative dermatitis, CBC ~ complete blood cell count; CXR = chest X-ay: ‘Some patients develop involvement of their hair and nails. Scaling of the scalp, alopecia, and in some cases, diffuse ffluvium can be seen, Nail changes may include “onycholysis, subungual hyperkeratosis, splinter hemor- rhages, paronychia, Beau's lines, and, occasionally, ony chomadesis? Shoreline nails with alternating bands ‘of nail plate discontinuity represent drug-induced ED reflecting the periods of time the drug was used.” ‘Sparing of the nose and paranasal areas (the “nose sign”) has been described in some studies. Arcolar sparing has been noted in some cases of CICL, drug reactions, “eczema,” psoriasis, photosensitivity, and PRP2 Typically, there is not mucosal involvement. Eruptive sebortheic keratoses may arise in patients with ED" The keratoses often resolve spontane ‘ously as the ED subsides. ‘The cutaneous lesions may suggest the underlying ctiology of ED. For example, in early psoriatic ED, clas sic psoriatic plaques may be seen. Gottzon’s papules, heliotrope rash, and muscle weakness may be pres: tent in ED caused by dermatomyositis. Papulocryth- roderma of Ofuji typically spares the abdominal skin folds the “deck chaie” sign). Figure 23-3 Blepharit's, epiphora, and ectropion in atopic exfoliative dermatitis amuon2as uone|nBaishg pue Ayan2eay |j2D- Uo paseg srapiosiq Alo,euWueyU 272 Pelagia to Peas. Features of underlying diseases may aid in diagnosis (see Table 23-3 and eFiguees 23-4.1-23-4.4in online edition). Gi adel a Related physical findings due to ED of any etiology: may include the following * Tachycardia duc to increased blood flow tothe skin and fluid loss due to disrupted epidermal barrier, High-output cardiac failure has been infrequently. reported secondary to the high-flow state in ED. ‘Thermoregulatory disturbances can result in hyper thermia or less commonly hypothermia; however, ‘most patients complain of feeling chilly, ‘Generalized lymphadenopathy occurs in more than ‘one-third of patients.*” The clinician must distin {guish between dermatopathic lymphadenopathy and lymphoma, If lymphadenopathy is prominent, ‘lymph node biopsy may be required. Hepatomegaly may occur in about one-third of patients ** and is more commonly seen in drug induced ED. Splenomegaly has also been rarely reported” and is ‘most commonly associated with lymphoma, Peripheral pedal or pretibial edema may occur in ‘up to 34% of patients” Rarely facial edema has been reported in drug-induced ED. edie MaU Led Laboratory tests are most often not diagnostic and not specific. Common laboratory abnormalities found in ED patients include anemia, leukocytosis, Iympho- Figure 23-4 Pityriasis rubra pilars exfoliative dermatitis with keratoderma, Note keratoderma with an orange hue and thickening of the thumbnail, ‘eytosis, eosinophilia, increased IgE, decreased serum albumin, and an elevated erythrocyte sedimentation rate, Fluid loss may lead to electrolyte abnormali- ties and abnormal renal function (elevated creatinine level). Elevated IgE levels have been noted in patients with ED unrelated to atopic dermatiis,”"=™ including. ‘of psoriatic ED patients." Eosinophilia is non- icand has been found in 20% of ED patients However, when highly elevated eosinophil counts are noted, the possibility of associated Hodgkin disease must be investigated Its very important to differentiate benign erytiaro- ermic inflammatory diseases from Sézary syndrome. In cases where erythrodermic CTCL is suspected, a thorough evaluation of skin, blood, and Iymph node samples is required for definitive diagnosis. Studies have shown that a level of 20% or more circulating, Sézary cells is a useful diagnostic criterion for Sézary syndrome, whereas less than 10% is nonspecific. Exceptions do occur, such as in certain severe drug juced reactions that can mimic Sézary synceome (as hydantoin hypersensitivity) Several benign derma- toses, including psoriasis, atopic dermatitis, discoid lupus, lichen planus, and “parapsoriasis” show the presence of Sézary cells in numbers less than 10%. Demonstration of a clonal T cell receptor gene rear- rangement is recommended for a sensitive and specific differentiation of Sézary syndrome from other etiolo- gies of ED. Ina recent study, quantitative real-time polymerase chain reaction analysis ofthe expression values of five genes [(1) STATS, 2) GATA-3, 8) PLS3, (4) CDID, and (6) TRAIL] has proven useful for molecular diagno- sis of Sézary syndrome" (see Chapter 143). Several molecular markers of Sézary cells have been recently studied (Tivist, EphAd, Teplastin). In one report, CDISBK/KIRSDL2, akiller_ immunoglobulin-like receptor normally expressed by subsets of circulating ‘T CD8+ lymphocytes and natural killer cells, has beenA Underlying Disease Process Idiopathic eryhroderma Cred man synerome’) Psoriasis (se Chapter 18) ‘topic dermanis se Chapter 14) Spongiotic dermatitis of other ‘tologies such as contact erat (ee Chapter 13) (eg. 25-11 online edition) or stasis Germattis (ee Chapter 174) Drug reaction see Chapter 41) Cutaneous Feellymphoma (see Chapter 145) Immunobullous disease Perahigus foliaceus andfoge selvagem (ee Chapter 54) Bullous pemphigoid (see Chapter 6) Parancoplatie pemphigus (see Chapters8) Paraneoplastic Pryrasis rubra plas ie Caper 26) (Chron actinic dermatitis see CChapter81) Acute gatversuchos disease (see Chapter 28) Dermatomyositis (se Chapter 156) Sstcoldosis (ee Chapter152) [Norwegian seabies (see Chapter 208) ED = exfoliative dermats Clinical Clues Elderly men Pras Cronicand relapsing course Palmoplantar keratoderma Dermatopathic lymphadenopathy History of localized disease Personal fal history of psoriasis ‘Clasicpseriasfarm plaques on elbows, knees, Wiel-crcumscribed plaques at margins of enjthroderma (Fig. 23-43 in online edition) History of localized seas, most often moderate to severe Personal family history of atopy atopic derma, asthra, hinocenjunetvits) Marked pruritus Distribution of riginal skin lesions History of contactant Histor of preesisting venous dsease Recent start of new drug, or us of frequently implicated drug Rapid onset of rash and progression to exfoliative Dermatiis Severe debilitating pruritus Fisutes painful keratoderma Hepatesplenemegaly Faced blisters Collaretesof cleat sites of previous biters Superficial erosions and crusts Tense listers (atl lesions) Deep erosions and supercluleers Unica plaques Mucosal erosions and crusting prominent Rash eesembls erythema mutsforme Fallre to thive (cachexia) _Fallreto thrive (le, aches) Ina esion-seborteicdermailke eruption atthe scalp Worsening pestsun exposure Generalized salmon-coloed sight infrted cythema (fig, 23-44 onne edition) Photo-accentuation History of bone marrow transplantation oF blood transfusion ‘Gotton papules Helctope sign Poikloderms| ‘pale ely papules, plaques and/or nodules Bewnsdtome or naingheme pent "Features of underlying diseases maya in cages Large amelar sales Portnall changes pits, olrop sign, ‘onychobyss, subungual hyperkeratosis CColarettes of scale suggestive of ruptured pustules of pustular psoriasis Porte athe Classic atopic lesions ln antecustal and popliteal fossae Lchenifeation and prarig nedulais Excoriations Fecal skin atrophy rom years of use of potent topical steroids lymphadenopathy Srnromessy lymphadenopathy Nopecia Leonine facies Prue Elery patient lands of sparing eFg. 23-44 n online edition) Palmeplantar keratoderma, often orange F254) Folleulr pink papules of elbows, wits dorsal fingers arin skin spared rom ED. Ini eson- palmar enythems Progression to toxic epidermal necrolysis Periangual telangiectasia Muscle weakness Massively thickened nails Keratoderma 23