Healthy Baby Practical advice for treating newborns and toddlers.

“Making Lemonade” out of Lyme Stan L. Block, MD, FAAP

ractitioners often encounter peculiar round/oval in pe- P diatric patients, particularly dur- ing the warm-weather months. Most of these rashes are benign, and most are insect-related; but certain ones may be more ominous. In some regions of the country, bites are a year-round issue, but cases have been reported elsewhere in colder months, due to the frequent number of warm spells during the winter in which may emerge. Besides, soon enough the warm months of “lemonade-time” All images courtesy of Stan L. Block, MD, FAAP. Reprinted with permission. All images courtesy of Stan L. Block, MD, FAAP. and tick bites will be upon much of the Figure 1. A 3-cm, faint, oval, maculopapular annular concentric lesion with some clearing in posterior rest of us. Thus I thought this presentation of 3-month-old girl. The small central , or “punctum,” was the site of tick bite. “refreshing” some aspects of particularly benign-looking rashes — with especially faint, concentric 3-cm ovoid in the CASE TWO problematic outcomes if left untreated posterior axillary area (see Figure 1) that A previously healthy, white, 4-year- – would be worthwhile. As usual, these started yesterday. During a 3-day family old boy from central Kentucky comes to cases show that the synthesis of the his- camping trip at a Kentucky state park the your office with a rash that has slowly tory with the physical findings is critical. previous weekend, the mother noticed a progressed across his back since having small black dot under the baby’s axilla, a “tiny” tick removed. His mother reports CASE ONE which she scraped off with much dif- the boy constantly plays outside on his A previously healthy, white, 3-month- ficulty. The baby’s immunizations are family’s farm and that the tick was on old girl presents to your office with a up to date, she has been healthy, and is the boy’s back for 7 days before it was growing well. There are no other symp- removed 3 days prior to the office visit. Stan L. Block, MD, FAAP, is Professor of Clinical toms such as pruritus, , cough, rhi- Since the removal of the tick, the annu- Pediatrics, University of Louisville, and University of norrhea, or fussiness. Her physical exam- lar rash has enlarged to 5 cm in diameter Kentucky, Lexington, KY; President, Kentucky Pedi- ination is otherwise unremarkable; there with central clearing, a maculopapular atric and Adult Research Inc.; and general pediatri- is no fever and the range of motion in her border, and a central punctum bite (see cian, Bardstown, KY. neck and joints is normal. The mother Figure 2, page 58). The boy has been Address correspondence to Stan L. Block, MD, remarked that the day after the camping healthy recently and is fully vaccinated. FAAP, via email: [email protected]. trip, she removed a lot of “tiny little dark He has no complaints of pruritus or pain Disclosure: Dr. Block has disclosed no relevant ticks” from her 4-year-old son. Could a with the rash, and also denies sore throat, financial relationships. 3-month-old child develop an arthropod- other rashes, , fever, arthralgias, doi: 10.3928/00904481-20130128-05 borne illness? and gastrointestinal symptoms.

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The mother demands that her son ing slightly feverish. Although her initial be tested for . Is this rash physical examination 5 days earlier was alone significant enough to be diagnostic normal, she now has some slight stiff- of an arthropod-borne illness? ness of her knees but no pain or redness of any joints. She is afebrile, her neck CASE THREE is supple, her retinal fundoscopic ex- A previously healthy, white, 3-year- amination reveals no papilledema nor old boy from central Kentucky sustained any blunting of the spontaneous venous a deer tick bite 8 days before coming to pulsations, and the remainder of the ex- your office. When removed, the tiny tick amination is normal. Figure 2. A white, 4-year-old boy with a 5-cm rash was noted to be engorged and still barely You were not aware of any report of with concentric round rim of raised maculopap- visible. Six days later, an oval rash started resistance to amoxicillin for ules surrounding a central punctum deer tick bite from 10 days earlier. on his left anterior chest region, which , but you do know that doxycy- has now enlarged to 3 cm by 6 cm over 2 cline is the preferred antibiotic for pa- days (see Figure 3). The punctum area of tients aged older than 8 years because it the tick bite now has some mild papular may have a higher noncomparative cure urticaria as well. The rash has a mostly rate than amoxicillin in adults (100% vs. flat border, some central clearing, and has 92%, respectively) and it covers anaplas- recently developed a tail of lymphangiitis mosis.1 Because she has now developed spreading posterior-laterally. The rash is some mild systemic symptoms but no not painful and only slightly pruritic. The true arthritis, you surmise that switching boy has been fully vaccinated. He denies to 100 mg twice daily for 14 any sore throat, arthralgias, , days would be prudent. Within 48 hours, neck stiffness, fever, other rash, or gas- she is remarkably better, and her arthral- trointestinal symptoms. His physical ex- gias and subjective fever had abated. amination is otherwise unremarkable. Does an arthropod-borne rash ever de- LYME DISEASE velop a mild lymphangiitis? Could there Epidemiology Figure 3. A white 3-year-old boy with a 3-cm by 6-cm, oval, 2-day rash with slightly raised rim sur- be two concomitant bacterial , Lyme disease, a zoonosis transmitted rounding small raised papular-urticarial punctum such as a lymphangiitis from a concomi- by the common deer tick ( scapu- deer tick bite from 8 days earlier. Note the faint 6-cm long, flat tail of redness spreading posterior- tant staphylococcal ? laris in the East and Midwest, and Ixo- laterally from rim of lesion. Slightly pruritic di- des pacificus in the West), is caused by rectly over the tick bite, the rash was not painful. CASE FOUR the bacterial spirochete, Borrelia burg- A previously healthy, white, 16-year- dorferi. of tick, Amblyomma americanum, can old girl from central Kentucky frequently When ticks attach, they appear as a transmit a “look-a-like” spirochetal in- walks outside in the woods of her fam- tiny, black or dark dot, similar to an el- fection that can cause a similar solitary ily’s land. Twelve days earlier, she re- evated on the skin. Of the 15,000 migrans rash and a self-limited moved a deer tick from her left bicep cases reported annually,1 the mid-Atlan- infection, known as southern tick-associ- area. Five days later she noticed the start tic, northeastern, and north central areas ated rash illness (STARI).2,3 The etiology of a small, red, slightly raised rash that of the United States account for 93% of of this lesion is unknown. Kentucky is was initially somewhat pruritic but never all reports of Lyme disease.2 Interesting- located on the same geographic latitude painful. It grew to about 5 cm by 5 cm by ly, Lyme disease is rarely reported south as Virginia, so in my opinion, all cases the time she presented to your office 2 of Virginia because ticks in southeastern of solitary must un- days later. You prescribed amoxicillin 1 states and southwestern states feed most- fortunately be considered as early Lyme g twice daily for 14 days. ly on reptiles rather than small mammals disease in our region. Just like the other Five days later, however, the rash had and deer.2 rarer arthropod-borne diseases, Rocky doubled in size (see Figure 4, page 59), Reptile blood is bacteriostatic for Mountain spotted fever and ehrlichiosis, and she now complained of arthralgias Borrelia, thus explaining the rare inci- the primary season for Lyme disease is of her knees, elbows, and neck, along dence of Lyme disease in the southern April through October, with the peak with mild headaches, malaise, and feel- US.1,3 However, the different species during the summer months.

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The incubation period for Lyme dis- ease is from 1 to 32 days, with a median of 11 days. Persons of any age can be in- fected, as we shall see in our discussion of Case One.

Stages of Lyme Disease There are three distinct stages of Lyme disease. It is notable that these stages are similar to those of another rar- er spirochetal infection, .1

Stage one: early localized disease Early localized Lyme disease presents with a solitary lesion, erythema migrans, in 80% to 90% of cases. It usually starts as a central small “punctum,” or papule, where the tick bite originated. It then spreads centrifugally to form a large an- nular or sometimes ovoid lesion usually 5 cm or larger, often accompanied by Figure 4. A rapidly spreading 10-cm, concentric, nonpruritic, round rash with raised maculopapular rash border, clearing around the punctum in a white, 16-year-old girl. The patient sustained a tick bite 12 central clearing. This lesion is usually days earlier. Despite amoxicillin therapy, the rash enlarged and the patient developed some systemic painless and nonpruritic but not always. symptoms and arthralgias. Erythema migrans can be differenti- ated from tick bite hypersensitivity. This grounds alone. Early treatment nearly large-joint, pauci-articular arthritis, usu- usually occurs either while the tick is still always aborts the development of later ally in the knees. attached or within 48 hours of detach- stages of Lyme disease. and central nervous system manifesta- ment. The hypersensitivity rash typically tions are rarely ever seen in children.2 begins to disappear within 1 to 2 days; is Stage two: early disseminated disease usually pruritic; and can sometimes be- If early Lyme disease is left untreated, DIAGNOSTIC TESTS come secondarily infected with Staphy- as it is in about 10% to 20% of children, The early stage of Lyme disease is di- lococcus or bacteria, caus- it will evolve into the secondary dis- agnosed strictly on the clinical observa- ing an , , lymphangiitis, seminated stage.2,3 This stage most com- tion of a solitary erythema migrans lesion or reactive lymphadenitis. Case Three is monly manifests several weeks, or occa- of at least 5 cm, with or without a history characteristic of a typical lymphangiitis sionally several days, after the tick bite of a deer tick attachment. Borrelia anti- from a tick bite. Lyme disease does not as multiple lesions of smaller erythema body titers are not detectable in most peo- cause these types of skin manifestations migrans. Other rare findings during this ple within the first 4 weeks following the by itself. The solitary erythema migrans stage include carditis manifested as mild appearance of erythema migrans.4 Once rash of Lyme will typically begin to to severe atrioventricular block, cranial treated appropriately, most patients will spread about 5 to 7 days after tick detach- nerve palsies (particularly of the 7th never develop antibodies. The develop- ment or removal, and the untreated rash cranial nerve—facial palsy), ophthalmic ment of antibodies after the treatment of will last about 3 weeks. conditions, and a subacute lymphocytic early stage Lyme disease, however, does But be aware that about 65% of pa- . Systemic symptoms are also not indicate therapy has failed.5 tients will also develop nonspecific much more prevalent and intense at this The biopsy and culture of the skin le- virus-like symptoms, such as malaise, stage, and include fever, headache, myal- sion is not recommended due to the dif- fatigue, neck pains, headache, migratory gia, arthralgia, and fatigue.2,3 ficulty with growing the culture from the arthralgias, chills, and fever.3 However, specimen. objective physical findings of frank ar- Stage three: late disease The diagnoses of early disseminated thritis are not present during stage one, This very rarely observed stage is disease and late disease should be made when a diagnosis is made on clinical characterized most commonly by a on the basis of both clinical appearance

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and serologic confirmation. Nearly all pa- fully to therapy except for Case Four. the lysis of the spirochetes treated with tients with later stage Lyme disease will penicillin? This reaction is reported in have detectable antibodies. This requires a Case One 15% of patients. It typically consists of two-step process for most laboratories.1,2 You were perplexed by the very young fever and chills within 24 hours of an- The first test consists of either an enzyme age of this patient with an early erythema tibiotic therapy, and is associated with immunoassay or an immunoflourescent migrans lesion. But all other indicators more intense systemic symptoms and an antibody assay. Only if this test is positive pointed to the Lyme diagnosis, including increase in size and intensity of erythema or equivocal should a Western immunob- the deer tick removal, the timing of the of the skin lesion. The rash will eventu- lot test be performed for confirmation. rash’s appearance several days later and ally resolve in 7 to 14 days.2 Thus, in this not immediately (tick hypersensitivity), case, a 10% antibiotic failure rate must TREATMENT OF EARLY STAGE the punctum, the central clearing, and be contrasted with a 15% Jarisch-Herx- LYME DISEASE the raised border. The down-side of non- heimer reaction rate. Because this rash Early Localized Disease treatment was too consequential because worsened despite 5 days of amoxicillin According to the American Academy of high morbidity, and the risk of anti- therapy, you surmise this patient was an of Pediatrics (AAP) 2012 Red Book, biotic treatment was miniscule. antibiotic failure. “Antimicrobial therapy for nonspecific For initial antibiotic failures with symptoms or for asymptomatic seroposi- Case Two early stages of Lyme, a repeat course of tivity is discouraged.”2 Doxycycline is Despite your objections and clear ex- a different appropriate oral antibiotic for the preferred antibiotic for those older planations to the child’s mother that se- 14 to 21 days is recommended. Finally, than 8 years; whereas amoxicillin is rologic titers were unnecessary for early for early disseminated Lyme disease, recommended for younger patients. Ce- localized Lyme disease, at her insistence, appropriate oral are still con- furoxime is recommended for those al- you obtained the serology. The acute sidered first-line therapy. Oral doxycy- lergic to penicillin; note that first-gener- Borrelia titer results were negative, and cline for 21 days has been shown to be ation cephalosporins are not effective for the child did fine, with total resolution of as comparably effective as intravenous B. burgdorferi. Azithromycin is less ef- the rash in a few days. ceftriaxone for the same duration. Hos- fective and is not recommended as first- pitalization and intravenous therapy with line therapy. Duration of beta-lactam Case Three ceftriaxone is only indicated for symp- and doxycycline therapy should be for at Despite a fairly typical solitary ovoid tomatic patients with meningitis, cardi- least 14 to 21 days. erythema migrans lesion, this child most tis, second- or third-degree atrioventricu- Erythema migrans usually resolves likely had a secondary bacterial infection lar (AV) block, or first-degree AV block within a few days of antibiotic therapy, of the tick bite with a mild ascending lym- with a very prolonged PR interval (≥ 300 but other low-grade phangiitis from either a staphylococcal milliseconds). may persist for weeks to months de- or streptococcal infection. In hindsight, spite successful therapy. In fact, fatigue amoxicillin clavulanate or cefuroxime REFERENCES and arthralgias may persist for up to 3 may have been better choices because of 1. Feigin RD, Cherry J, Demmler-Harrison GJ, Kaplan SL (eds). Feigin and Cherry’s Textbook months in 25% of adequately treated pa- their methicillin-sensitive Staphylococ- of Pediatric Infectious Diseases. 6th edition. tients; 10% of adults do not respond to cus aureus coverage. The most important Philadelphia, PA: Saunders Elsevier; 2009. therapy.3 For further specific antibiotic factor in atypical cases is the careful fol- 2. AAP Committee on Infectious Diseases; Pick- ering LK, Baker CJ, Kimberlin DW, Long SS dosing regimens and for management of low-up over the next several days. (eds). Red Book: 2012. Report of the Commit- early disseminated disease and late dis- tee on Infectious Diseases (Red Book Report ease, refer to the 2012 AAP Red Book.2 Case Four of the Committee on Infectious Diseases). 29th edition. Elk Grove Village, IL. American Acad- You initially thought that the contin- emy of Pediatrics; 2012. DISCUSSION OF CASES ued spread and new onset of systemic 3. Wormser GP. Lyme disease. In: Goldman L, Each of the four cases presented a symptoms 5 days into therapy most Schafer AI (eds). Goldman’s Cecil Medicine. peculiar diagnostic aspect of Lyme dis- likely indicated a failure while on amox- 24th edition. Philadelphia, PA: Saunders Else- vier; 2012. ease. All four cases were treated with icillin therapy. Up to 10% of adults do 4. Tibbles CD, Edlow JA. Does this patient have appropriate doses (50 mg/kg/day to 90 not respond to initial antibiotic therapy. erythema migrans? JAMA. 2007;297:2617- mg/kg/ day, with a maximum dose of 1 However, one caveat: Could she have 2627. 5. Steere AC, McHugh G, Damle N, Sikand VK. g) of amoxicillin twice daily, and each possibly experienced a Jarisch-Herx- Prospective study of serologic tests for Lyme patient responded rapidly and unevent- heimer–like immunologic reaction from disease. Clin Infect Dis. 2008;47(2):188-195.

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