DOI: 10.1542/pir.32-8-3532011;32;353Pediatrics in Review 

Rosenthal, Pauline Henry, Danny Gahzarian, Erich Maul and Lakshmi MoorthyAlexandra Balma-Mena, Jillian Miller, Jennifer McGuirl, Miriam Weinstein, Alana

Ulcers in a 6-year-oldPolyarthritis, Raynaud Phenomenon, Hoarseness, Tapering Fingers, and DigitalRash in an 8-year-oldCase 2: Cough With Green Phlegm in an 8-year-oldCase 3: Index of SuspicionCase 1: Pruritic, Erythematous, Papular, and Papulovesicular

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The reader is encouraged to writepossible diagnoses for each case beforeturning to the discussion.

The editors and staff of Pediatrics in

Review find themselves in the

fortunate position of having too many

submissions for the Index of Suspicion

column. Our publication slots for Index

of Suspicion are filled through 2013.

Because we do not think it is fair to

delay publication longer than that, we

have decided not to accept new cases

for the present. We will make an

announcement in Pediatrics in Review

when we resume accepting new cases.

We apologize for having to take this

step, but we wish to be fair to all

authors. We are grateful for your

interest in the journal.

Author Disclosure

Drs Balma-Mena, Weinstein, Rosenthal,

Henry, Gahzarian, Miller, Maul,

McGuirl, and Moorthy have disclosed

no financial relationships relevant to

these cases. This commentary does not

contain a discussion of an unapproved/

investigative use of a commercial

product/device.

Case 1: Pruritic, Erythematous, Papular, andPapulovesicular Rash in an 8-year-old

Case 2: Cough With Green Phlegmin an 8-year-old

Case 3: Polyarthritis, Raynaud Phenomenon,Hoarseness, Tapering Fingers, and DigitalUlcers in a 6-year-old

Case 1 PresentationAn 8-year-old boy presents with a3-week history of red, itchy, raisedlesions that developed vesicles andblack crust. The lesions started onthe neck and inguinal region but be-came generalized within a few days.He was diagnosed as having varicellaand sent home with symptomaticmanagement. A few days later, hewas seen in the ED because of feverand persistence of the eruption. Hewas prescribed oral cephalexin for apossible secondary infection of thevaricella. He has not improved and isfinally admitted to a regional hospitalfor further evaluation.

Physical examination shows ageneralized eruption of erythema-tous papules, most of which have adark crust in the center, as well as afew papulovesicles on the extremi-ties, including the palms and soles(Fig. 1). He has enlarged inguinal

nodes and complains of intense pru-ritus. The differential diagnosis in-cludes varicella, herpesvirus infec-tion, and vasculitis.

Results of laboratory studies in-clude:

● WBC count: 4.0�103/�L (4.0�109/L) with normal percentagesand absolute numbers of lympho-cytes and neutrophils

● Hgb: 12.9 g/dL (129 g/L)● Platelet count: 349�103/�L (349

�109/L)● Creatinine: 0.5 mg/dL (44.2

�mol/L)● BUN: 8 mg/dL (2.9 mmol/L)● ALT: 9 U/L (normal, 0 to

41 U/L)● Alkaline phosphatase: 200 U/L

(normal, �300 U/L)● C-reactive protein: 0.7 mg/dL

(normal, �1 mg/dL)

Figure 1. Eruption consisting of erythematous papules, most of which have a darkcrust in the center, and a few papulovesicles on the right lower extremity.

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● ESR: 22 mm/hr (normal, 0 to10 mm/hr)

Urinalysis is negative for proteinand erythrocytes and a urine cultureis sterile. Results of bacterial cultureand polymerase chain reaction test-ing for herpes group viruses from theskin lesions are negative. Additionalevaluation leads to the diagnosis.

Case 2 PresentationAn 8-year-old boy who has a historyof recurrent pneumonia, CHARGEassociation, repaired tetralogy ofFallot, gastroesophageal reflux dis-ease, and severe kyphoscoliosis pres-ents with the production of greensputum and increasing work ofbreathing for 5 days. He is afebrilebut is coughing and has tachypneaand copious rhinorrhea. His familydenies other symptoms or sick con-tacts. He has a 5-year history of re-current pneumonia, which has oc-curred more frequently over the past6 months. He has been treated with

multiple courses of oral and paren-teral antibiotics.

Physical examination reveals atemperature of 37.0°C, heart rate of140 beats/min, respiratory rate of 40breaths/min, blood pressure of110/74 mm Hg, and pulse oximetryreading of 94% in room air. He doesnot appear toxic and has copiousthick nasal secretions. Auscultationreveals clear right lung fields andbronchial breath sounds and rhonchion the left, especially over the lowerlobe of the lung. Upper and lowerextremities appear acyanotic withdigital clubbing.

Results of his CBC and metabolicpanel are normal. His C-reactive pro-tein measures 1.1 mg/dL. Chest ra-diography reveals a clear right lungwith nearly complete opacification ofthe left hemithorax, an unchangeddextroscoliosis, and no mediastinalshift. Bronchoscopy demonstratesnormal anatomy with diffuse tra-cheobronchitis and mucus pluggingof bronchi in the left lung. An addi-tional imaging study helps establishthe diagnosis.

Case 3 PresentationA 6-year-old African American girlwho has been suffering from polyar-thritis for the past 2 years presentswith the recent onset of increasingfatigue, new-onset Raynaud phe-nomenon, hoarseness, worseningarthritis, tapering fingers, digitalulcers, and tightening of the skinover her fingers. She has had mini-mal response to nonsteroidal anti-inflammatory agents (NSAIDs),methotrexate, and etanercept in thetreatment of her arthritis. She reportsan episode of fever and pericardialeffusion a few months earlier thatresponded to a course of corticoste-roids.

Physical examination reveals atired-appearing, thin girl in no acute

distress. She has tapering fingers withskin tightening; periorbital telangiec-tasias; round healing ulcers on hersecond finger tip and second, third,and fourth proximal interphalangeal(PIP) and metacarpophalangeal(MCP) joints; and nailfold capillarychanges. She has calcinosis over herleft arm and right knee and tighten-ing of the skin over her hands andknees bilaterally. Subcutaneous nod-ules are apparent over her left elbowand right knee. She has polyarthritisinvolving both knees, hips, wrists,and PIP and MCP joints.

Laboratory studies reveal:

● Hgb: 10.4 g/dL (104 g/L)● Antinuclear antibody (ANA) titer:

1:640● Rheumatoid factor (RF) titer: 34● Antiribonucleoprotein (RNP) an-

tibody: positive● Lactate dehydrogenase: 439 U/L

(7.3 �kat/L)● Creatine kinase: 58 U/L (0.96

�kat/L)● Aldolase: 12.5 U/L (0.21 �kat/L)● ESR: 85 mm/hr

Serum complement concentra-tions, WBC count, platelet count,complete metabolic panel, and uri-nalysis findings are within normallimits. Antidouble-stranded DNA,anti-Smith, anti-Jo, anti- SSB, anti-Scl-70, and anti-centromere anti-body determinations are negative.Echocardiography shows a resolvingpericardial effusion, and ECG find-ings are within normal limits. Pulmo-nary function tests reveal a decreasein diffusion lung capacity (DLCO).

Case 1 DiscussionThree skin biopsies were sent for his-topathologic examination. Two bi-opsies from the knee and one fromthe elbow showed similar findingsconsistent with a diagnosis of pityri-asis lichenoides et varioliformis acuta

Frequently Used Abbreviations

ALT: alanine aminotransferaseAST: aspartate aminotransferaseBUN: blood urea nitrogenCBC: complete blood countCNS: central nervous systemCSF: cerebrospinal fluidCT: computed tomographyECG: electrocardiographyED: emergency departmentEEG: electroencephalographyESR: erythrocyte sedimentation

rateGI: gastrointestinalGU: genitourinaryHct: hematocritHgb: hemoglobinMRI: magnetic resonance imagingWBC: white blood cell

index of suspicion

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(PLEVA). The boy was started on an8-week course of oral erythromycinand was followed in the dermatologyclinic, where his skin showed consid-erable improvement (Fig. 2). He hashad no recurrence.

The ConditionPLEVA is an uncommon dermato-logic condition of unknown causethat was described initially by Neisserand Jadassohn in 1894. (1)(2) It canaffect both children and adults andhas been reported to be associatedwith infectious triggers, immunecomplexes, and lymphoproliferativeprocesses.

The two clinical forms describedare PLEVA and pityriasis lichenoideschronica (PLC). This classification isbased on the duration of the episodeand different clinical presentations.PLEVA is characterized as papular orvesicular lesions with central necro-sis, while PLC has thinner papuleswith scale that leave behind charac-teristic white macules. PLC has nocentral necrosis or vesicles and is amore chronic eruption. Some au-thors argue that PLEVA and PLCrepresent a clinicopathologic spec-trum rather than independent dis-eases.

PLEVA is characterized clinicallyby the acute onset of erythematouspapulovesicles with ulceronecroticcenters. These lesions can result invarioliform scars and postinflamma-tory hypo- or hyperpigmentation.The eruption is polymorphous andpresents more frequently on the ex-tremities and flexural areas. Affectedpatients complain of pruritus and aburning sensation. The differentialdiagnosis of PLEVA includes vari-cella, arthropod bites, viral exan-thems, lymphomatoid papulosis, andvasculitis.

The histopathologic features ofPLEVA consist of a perivascular andoften wedge-shaped interstitial lym-

phocytic infiltrate with interface der-matitis features of exocytosis andbasal cell vacuolation. Other findingsinclude red blood cell extravasation,variable keratinocyte necrosis, andoverlying parakeratosis, with crustformation possible.

ManagementPLEVA generally is considered a be-nign process that has a self-limitedcourse of several weeks. Differenttreatments have been described, in-cluding topical corticosteroids andtopical tacrolimus, which evoke agood response. Oral antibiotics thathave anti-inflammatory properties,such as erythromycin, tetracycline,and azithromycin, administered for8 weeks also have produced goodresponses. For cases of extensive in-volvement, ultraviolet B photother-apy is effective in children.

The prognosis of PLEVA is good,with a more benign course occurringin children than in adults. A few re-ports in the literature show progres-sion to cutaneous T-cell lymphoma,which is why close monitoring is rec-ommended.

Lessons for the Clinician

● PLEVA should be considered inthe differential diagnosis of vesicu-lar, papular, and papulovesiculareruptions in children.

● For a patient who has vesicular le-sions and systemic symptoms,other conditions such as varicellaand herpes infection should beruled out.

● A skin biopsy is needed to confirmthe diagnosis of PLEVA and to ruleout other entities.

● Management includes an 8-week

Figure 2. Considerable improvement of the skin after an 8-week course of oralerythromycin.

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course of anti-inflammatory antibi-otics, which produces a good re-sponse. The prognosis in the pedi-atric population usually is good.

(Alexandra Balma-Mena, MD, Mir-iam Weinstein, MD, Alana Rosen-thal, MD, Hospital for Sick Children,Toronto, Ontario, Canada; PaulineHenry, MD, University of Toronto,Toronto, Ontario, Canada; DannyGahzarian, MB ChB, PhD, FRCPC,FCAP, University Health Network,Toronto, Ontario, Canada)

References1. Neisser A. Zur frage der lichenoideneruptionen. Verh Dtsch Dermatol Ges. 1894;4:495–5062. Jadassohn J. Uber ein eigenartiges psori-asiformes und lichenoides exanthem. VerhDtsch Dermatol Ges. 1894;4:524–535

Case 2 DiscussionNoncontrast, high-resolution com-puted tomography (HRCT) scan ofthe chest revealed marked bronchiec-tatic changes of the entire left lung(Fig. 3). The boy underwent leftpneumonectomy, and pathologic ex-amination showed massive bronchi-ectasis in the upper and lower lobes,with a very small amount of normalintervening parenchyma within theleft lung.

The ConditionBronchiectasis is caused by destruc-tion of the bronchial wall. Loss ofintegrity of the muscular and elasticlayers of the bronchial wall results inan easily collapsible airway and ob-structed sections of the bronchialtree. The first stages of change in-clude mucosal wall thickening andmild airway dilation, referred to ascylindrical bronchiectasis. If the un-derlying cause can be treated effec-tively in the early stages, the degreeof bronchiectasis may be controlled.

Once the disease progresses, thebronchi become tortuous and bal-looned, a condition known as saccu-lar bronchiectasis, which is consid-ered irreversible.

Although cystic fibrosis (CF) isthe most common cause of bronchi-ectasis in children in the UnitedStates, several other conditions mustbe considered. These can be dividedinto disorders causing fixed obstruc-tion, diseases affecting the integrityof bronchial wall and mucus clear-ance, and infections.

Airway obstruction compromis-ing mobilization of secretions fromthe tracheobronchial tree can be asource of bronchiectasis. Airway ob-struction can result from severe ky-phoscoliosis; a retained foreign body,intraluminal tumor, or other mass;lymphadenopathy; vascular anomaly;or cardiac pathology that results inairway impingement.

If mucociliary clearance is com-

promised, even in the absence of air-way obstruction, bronchiectasis canresult. In patients who have CF, thetenacity of the secretions and the rel-atively diminished amount of fluid inthe airway lining makes mobilizationof secretions from the lower airwaysdifficult. Similarly, diseases in whichmuscle strength is compromised,such as muscular dystrophy or spinalmuscular atrophy, can result in bron-chiectasis from compromised mobili-zation of lower airway secretions.Children who have compromised cil-iary function, such as occurs in pri-mary ciliary dyskinesias, generally areunable to mobilize secretions fromthe lower airways and may developbronchiectasis.

Infection of the secretions in theairway distal to either the anatomicor functional obstruction plays a crit-ical etiologic role. Hence, diseasestates that entail immunodeficienciesor abnormalities in neutrophil func-

Figure 3. Noncontrast, high-resolution computed tomography scan of the chestshows diffuse saccular bronchiectasis of the left lung with a mediastinal shift to theleft.

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tion can lead to bronchiectasis.Among the most frequent causes ofbronchiectasis in children are disor-ders such as hypogammaglobuline-mia, abnormalities of the respiratoryburst in neutrophils, complementdeficiencies, selective immunoglobu-lin deficiencies, and acquired immu-nodeficiency syndrome.

Regardless of the primary cause,infection is the final factor in the de-velopment of bronchiectasis, and thelikelihood of developing bronchiec-tasis increases with prolonged anduntreated infections. The pathogenscausing bronchiectasis generally arebacteria such as Pseudomonas aerugi-nosa, Mycobacterium tuberculosis,Mycoplasma pneumoniae, or Strepto-coccus pneumoniae. However, the in-fection may be viral, most commonlyadenovirus and influenza, or evenfungal.

Allergic bronchopulmonary asper-gillosis, a hypersensitivity pneumoni-tis that is associated most commonlywith CF, results in central saccularbronchiectasis.

In children, it may be difficult toidentify the cause of bronchiectasis,but every attempt must be made todo so to allow institution of appro-priate management.

Clinical ManifestationsCough and sputum production arethe most common symptoms ofbronchiectasis; dyspnea, rhinosinus-itis, and hemoptysis are less com-mon. Affected patients frequentlyhave received the diagnosis of recur-rent pneumonia. Physical examina-tion findings of bronchiectasis in-clude crackles, wheezing, andrhonchi; digital clubbing also may bepresent.

DiagnosisDiagnosis relies predominantly onimaging. Laboratory studies, such asCBC, quantitative immunoglobu-

lins, and sputum culture, may helpdetermine the cause but are nondiag-nostic alone. Chest radiograph mayreveal airway dilation, increased pul-monary markings with tram tracking(thickening of the bronchial walls),and areas of atelectasis. HRCT is thegold standard for diagnosis and re-veals detailed anatomy of the bron-chial tree: lack of airway taperingwith luminal dilation, bronchial wallthickening, honeycombing, and mu-cus plugging.

Treatment and PrognosisManagement should focus on identi-fying and treating the underlyingcause of the bronchiectasis. Estab-lishing the primary cause is of criticalimportance and is undertaken bestunder the direction of a pediatricpulmonologist. Following determi-nation of the cause, optimal manage-ment often involves a multidisci-plinary team, including primary carephysicians, pulmonologists, and re-spiratory therapists.

Decreasing acute exacerbationsby employing a regimented dailytherapy may slow disease progres-sion. Mucus clearance may be en-hanced with hypertonic saline nebu-lization, inhaled mucolytics, andchest physiotherapy. Inhaled cortico-steroids can reduce airway obstruc-tion. Chronic macrolide therapy alsohas been found to be beneficial. Inaddition to antimicrobial properties,macrolides have anti-inflammatoryproperties. Aggressive treatment ofpseudomonal and Staphylococcus au-reus infections is indicated, but anti-microbial therapy should be targetedto specific pathogens. Lobectomy is alast resort in refractory cases.

The efficacy of different treatmentmodalities for non-CF-associatedbronchiectasis is largely unknown atthis point and remains an area ofactive research. The prognosis fornon-CF bronchiectasis depends on

the cause and the patient’s access tomedical care. Regular access to amultidisciplinary team facilitates ag-gressive treatment of exacerbations,emphasizes prevention, and allowsfor teaching self-management as wellas for monitoring and early interven-tion for comorbid conditions.

Lessons for the Clinician

● Although primarily seen in patientswho have CF, bronchiectasis is acondition that clinicians may needto consider when evaluating a childwho has a chronic cough.

● HRCT is vital to making the diag-nosis.

● Treatment protocols and therapiesare fairly well established for CFpatients but not for non-CF bron-chiectasis.

● A multidisciplinary approach, in-cluding the primary care clinician,pulmonologist, and allied healthclinicians, is crucial for manage-ment.

(Jillian Miller, MD, Erich Maul, DO,Kentucky Children’s Hospital, Lex-ington, KY)

Case 3 DiscussionThis young girl’s disease process wasconsistent with mixed connective tis-sue disease (MCTD). MCTD is con-sidered an overlap syndrome that in-cludes clinical features of juvenilerheumatoid arthritis, scleroderma,systemic lupus erythematous (SLE),and dermatomyositis (DM) occur-ring in conjunction with high anti-body titers to an extractable nuclearantigen. Children who have MCTDmay progress to SLE-like orscleroderma-like disease. The tight-ening of the skin, digital ulcers, Ray-naud phenomenon, calcinosis,hoarseness, and decrease in DLCOsuggest that this girl’s condition is

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evolving into systemic scleroderma,also known as systemic sclerosis.

She was treated with hydroxy-chloroquine, methotrexate, cyclo-sporine, pentoxifylline, and cortico-steroids. She was followed closelywith frequent physical examinations,swallow studies, pulmonary and car-diac assessments, and laboratoryevaluations. Currently she has persis-tent symptoms of decreased jointmobility, increasing calcinosis, andincreased reflux suggestive of an earlyCREST syndrome (calcinosis, Ray-naud phenomenon, esophageal dys-motility, sclerodactyly, and telangi-ectasias) that also is referred to aslimited cutaneous systemic sclero-derma.

The ConditionMCTD is one of the least commonconnective tissue diseases. The meanage of onset is 11 years, but the con-dition occurs in children between theages of 4 and 16 years and is morefrequent in girls. Common clinicalmanifestations include polyarthritisand Raynaud phenomenon, nailfoldcapillary changes, and cutaneouschanges that may be suggestive ofSLE, DM, or scleroderma. Cardio-

pulmonary disease and esophagealdysmotility are reported infrequentlybut may result in significant morbid-ity. Nephritis is less common and lesssevere than that seen in SLE. Thesclerodermatous skin changes areslow to develop but often becomethe most prominent feature of thedisease late in the course.

As with the clinical manifesta-tions, the laboratory findings ofMCTD and systemic sclerosis evolveover time. Most patients have posi-tive ANA, RNP antibody, and RF.

TreatmentThe treatment of MCTD is guidedby strategies used in rheumatologicdiseases such as SLE, scleroderma,and DM. Therapy often is based onthe individual’s disease course andspecific organ involvement. Treat-ment options include corticoste-roids, NSAIDs, hydroxychloro-quine, methotrexate, vasodilators,and cytotoxic agents. All of theseagents have been used with varyingdegrees of success. Overall, most pa-tients who have MCTD survive intoadulthood after the diagnosis is es-tablished. Morbidity and mortalityare greatest in those who develop

either renal or pulmonary manifesta-tions.

Lessons for the Clinician

● MCTD is an evolving disease thatmust be monitored closely.

● Not all polyarthritis is juvenile id-iopathic arthritis; other diagnosesshould be considered when the dis-ease does not respond to standardmedications.

● Systemic sclerosis is insidious inonset and often presents diagnosticchallenges, mandating close obser-vation and follow-up evaluation.

● Rheumatic diseases can have signif-icant overlap in clinical manifesta-tions, necessitating careful evalua-tion to determine that the correctdisease process is being treated.

(Jennifer McGuirl, DO, Departmentof Pediatrics, Goryeb Children’s Hos-pital, Atlantic Health, Morristown,NJ; Lakshmi Moorthy, MD, Depart-ment of Pediatrics, UMDNJ/RWJMedical School, New Brunswick, NJ)

To view Suggested Reading lists forthese cases, visit www.pedsinreview.org and click on Index of Suspicion.

index of suspicion

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DOI: 10.1542/pir.32-8-3532011;32;353Pediatrics in Review 

Rosenthal, Pauline Henry, Danny Gahzarian, Erich Maul and Lakshmi MoorthyAlexandra Balma-Mena, Jillian Miller, Jennifer McGuirl, Miriam Weinstein, Alana

Ulcers in a 6-year-oldPolyarthritis, Raynaud Phenomenon, Hoarseness, Tapering Fingers, and DigitalRash in an 8-year-oldCase 2: Cough With Green Phlegm in an 8-year-oldCase 3: Index of SuspicionCase 1: Pruritic, Erythematous, Papular, and Papulovesicular

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