Lyme Disease in Children.

Lyme disease is now the most frequently reported vector-borne disease in the United States. The highest incidence is in children aged 5 to 9 years with a male predominance. The most common manifestation, erythema migrans, is sometimes not recognized, leading to risk of complications. Testing for Lyme disease should only be done if there is a consistent clinical syndrome with exposure in a Lyme-endemic area. Most forms of Lyme disease are successfully treated with short courses of oral therapy. Prevention and management of tick bites is important.

Annular infectious dermatoses.

Annular configuration is conspicuous in the clinical manifestation of many skin diseases and can be helpful for the diagnosis and differential diagnosis. Variations may include arciform, ring-form, annular, circinate, serpiginous, gyrated, polycyclic, targeted or figurate forms, in different colors, sizes, and numbers, with various textures and surfaces. In infectious dermatoses, the annular reactions can be specific or nonspecific, while the underlying mechanisms remain largely unknown. In the specific reactions caused by direct invasion of the pathogens, the contest between the centrifugal outspread of the infectious agents and the centripetal impedance of the host immune response is supposed to determine the final conformation. Examples include erythema infectiosum, orf, erythema multiforme, and pityriasis rosea of viral origin. Bacterial infections that may display annular lesions include erythrasma, erythema (chronicum) migrans of Lyme borreliosis, secondary syphilis, cutaneous tuberculosis, and leprosy. Superficial mycosis, such as dermatophytosis, candida intertrigo, tinea imbricata, and subcutaneous mycosis, such as chromoblastomycosis, and algae infection protothecosis, are characterized by annular progression of the skin lesions. The creeping serpiginous extension is an alarming sign for the diagnosis of cutaneous larva migrans. A better understanding of the virulence and pathogenicity of the pathogens and the way and type of immune response will help to clarify the pathogenesis.

Erythema Migrans and Interface Changes: More Than a Fortuitous Association.

The histology of erythema (chronicum) migrans (ECM) is classically described as a nonspecific perivascular infiltrate with a variable number of plasma cells and eosinophils. However, deviations from this pattern were described, such as focal interface changes or spongiosis, potentially posing a clinicopathological challenge. In this study, cases submitted with a serologically confirmed, clinically unequivocal, or highly suspicious diagnosis of ECM/Lyme disease between January 01, 2016, and September 01, 2018, were retrieved from the electronic database system and reviewed to delineate the histopathologic features of ECM. The series consisted of 14 cases. A superficial perivascular lymphocytic infiltrate was noted in all biopsies, accompanied by a deep and/or interstitial inflammatory infiltrate in 9 cases (64%). The inflammation ranged from relatively sparse to dense and prominent. At least focal interface changes were noted in 12 biopsies (86%). Eosinophils and plasma cells were noted in 7 (50%) and 10 (71%) cases, respectively. From a histologic standpoint, ECM is a protean entity and may manifest with a variable density of perivascular and/or interstitial lymphocytic infiltrate admixed with eosinophils and/or plasma cells and accompanied by focal interface dermatitis. Within the appropriate clinical context, ECM should be considered in the differential diagnosis of focal interface and/or sparse perivascular dermatitis.

[Loss of motoric function in a three-year-old boy with lysosomal storage disease].

This case report describes a three-year-old boy with delayed development of language, who developed erythema migrans. Soon after peroral antibiotics was initiated, he also had loss of motoric function, and he developed ataxia. Neuroborreliosis was diagnosed, and antibiotic treatment was changed to intravenous. There was no gain of his motoric skills. A test was made for lysosomal storage disease, and neuronal ceroid lipofuscinosis type 2 was found. The patient started intraventricular enzyme substitution treatment as the first patient in Denmark. Treatment has shown to reduce the progression of functional decline.

Evaluation of Prospectively Followed Adult Patients with Erythema Migrans Using the Beck Depression Inventory Second Edition.

BACKGROUND: The Beck Depression Inventory (BDI-II) may be used to evaluate individuals for symptoms of depression. METHODS: In a 1-year prospective study, 52 adult Lyme disease patients with erythema migrans and 104 matched control subjects were clinically assessed and completed the BDI-II at study entry and approximately 6 and 12 months later following antibiotic treatment. RESULTS: The mean BDI-II score was significantly higher at the baseline visit among Lyme disease patients compared with controls (P = .002), but no significant differences between the groups were observed at either the 6- or 12-month study visits. Over the course of the study, the mean BDI-II scores decreased an average of approximately 0.22 points per month (P < .0005) for Lyme disease patients, whereas the mean scores changed very little for controls (mean change = -0.02 per month, P = .50). The total number of somatic symptoms, of the 12 symptoms evaluated, strongly and directly correlated with the BDI-II scores at the baseline visit for the Lyme disease patients. CONCLUSIONS: The mean BDI-II scores of patients with early Lyme disease significantly exceeded that of matched controls at study entry, but by 6 months the values did not differ significantly. There was a good-to-excellent direct correlation between the BDI-II score and the total number of symptoms, suggesting that the BDI-II scores were reflecting somatic rather than affective depressive symptoms. When using the BDI-II as an assessment tool of patients with Lyme disease, infection-related somatic symptoms per se need to be considered in the interpretation of the results.

Comparison of Clinical Course and Treatment Outcome for Patients With Early Disseminated or Early Localized Lyme Borreliosis.

Importance: Multiple erythema migrans (MEM) has been suggested as a risk factor for unfavorable antibiotic treatment outcome compared with solitary erythema migrans (EM). However, no direct comparison of early Lyme borreliosis manifested as MEM with solitary EM has been undertaken. Objective: To investigate the potential differences in clinical course and treatment outcome between MEM and solitary EM. Design, Setting, and Participants: This prospective cohort study was conducted from June 1, 2010, to October 31, 2015, at the University Medical Center Ljubljana, Slovenia. Data were analyzed from June 1, 2017, to January 3, 2018. Of the 778 consecutive adult patients with early Lyme borreliosis evaluated, 200 patients with MEM and 403 patients with solitary EM were enrolled. Patients were asked to refer a family member or a friend of similar age (±5 years) without a history of Lyme borreliosis to serve as a control participant. Clinical course and posttreatment outcome of MEM were compared with those of solitary EM. Outcome was assessed at 14 days and at 2, 6, and 12 months after enrollment. At each visit, patients completed a written questionnaire about their symptoms; controls completed the same questionnaire. Nonspecific symptoms reported by patients and controls without a history of Lyme borreliosis were compared. Main Outcomes and Measures: The proportion of patients with incomplete response at 12 months after enrollment and the associated 2-sided 95% CI for the difference between MEM and solitary EM were estimated using the normal approximation with continuity correction. Results: A total of 200 patients with MEM and 403 patients with solitary EM were included. Among the 200 patients with MEM, 94 (47.0%) were males and 106 (53.0%) were females, with a median (interquartile range [IQR]) age of 47 (35-58) years. Among the 403 patients with solitary EM, 182 (45.2%) were males and 221 (54.8%) were females, with a median (IQR) age of 55 (42-62) years. Patients with MEM reported Lyme borreliosis-associated constitutional symptoms at enrollment more often than those with solitary EM (93 [46.5%]; 95% CI, 39.4-53.7 vs 96 [23.8%]; 95% CI, 19.7-28.3; P < .001). During the initial 6 months after treatment, the proportion of patients with incomplete response was higher in the MEM group than in the solitary EM group (14 days: 62 of 193 [32.1%] vs 72 of 391 [18.4%]; P < .001; 2 months: 38 of 193 [19.7%] vs 55 of 394 [14.0%]; P = .28; 6 months: 29 of 182 [15.9%] vs 31 of 359 [8.6%]; P = .02). However, at the 12-month visit, the outcome was comparable: 10 of 170 (5.9%) patients with MEM vs 20 of 308 (6.5%) patients with solitary EM showed incomplete response (-0.6; 95% CI, -5.5 to 4.3; P = .95). The frequency of nonspecific symptoms in patients was similar to that in controls. Conclusions and Relevance: The long-term outcome at 12 months after treatment was comparable, regardless of dissemination. Follow-up of at least 12 months after treatment is thus recommended for future studies that investigate post-Lyme borreliosis symptoms.

Doxycycline-induced photosensitivity in patients treated for erythema migrans.

BACKGROUND: Doxycycline is one of the recommended antibiotics for treating erythema migrans (EM). Since EM predominantly occurs during summer, the potential of doxycycline to induce photosensitivity is of concern. In studies on the efficacy of doxycycline for treating relatively small numbers of patients with EM, the reported frequency of photosensitivity has varied from none to 15%. The aim of this study was to elucidate the frequency and clinical symptoms of doxycycline-induced photosensitivity in a large cohort of patients with EM treated in a single medical centre. METHODS: Prospectively collected data on adverse events were analysed in adult patients with EM treated with doxycycline 100 mg twice daily for 10-15 days. RESULTS: Photosensitivity reactions ranging from itching and burning sensations to transient mild erythema of sun-exposed skin were documented in 16/858 (1.9, 95% CI 1.1-3.0%) patients and appeared from June to October with highest frequency in July. These adverse events were more frequent in patients treated for 14 or 15 days (16/750 [2.1%]; 95% CI 1.2-3.4%) than in those treated for 10 days (0/108 [0%]; 95% CI 0.0-3.4%); however, the difference was not significant (P = 0.24). Women were more often affected than men (13/475 [2.7%], 95% CI 1.5-4.6% versus 3/383 [0.8%], 95% CI 0.2-2.3%; P = 0.04). Of the 16 patients who developed photosensitivity, 13 did not adhere to the recommendation to avoid sun exposure. None of the patients had any long-term sequelae of photosensitivity. CONCLUSIONS: Photosensitivity reactions in adult patients with EM treated with doxycycline 100 mg twice daily for 10-15 days occurred rarely, were not severe, and had no long-term sequelae. TRIAL REGISTRATION: Registered at http://clinicaltrials.gov , Identifiers NCT00910715, May 28th 2009, NCT01163994, July 13th 2010 and NCT03584919, June 19th 2018 retrospectively registered.

Occurrence of erythema migrans in children with Lyme neuroborreliosis and the association with clinical characteristics and outcome - a prospective cohort study.

BACKGROUND: Erythema migrans (EM) is the most common manifestation of Lyme borreliosis (LB), caused by the spirochete Borrelia burgdorferi sensu lato. The infection can disseminate into the nervous system and cause Lyme neuroborreliosis (LNB), the second most frequent LB manifestation in children. The aim of this prospective cohort study is to describe the occurrence of EM among children with LNB and to evaluate possible differences in clinical characteristics or outcome between LNB patients with and without EM. METHOD: Children being evaluated for LNB in southeast Sweden during the period 2010-2014 underwent a clinical examination, laboratory testing and filled out a questionnaire regarding duration and nature of symptoms, EM and the child's health. Children were classified according to European guidelines for LNB. Clinical recovery was evaluated at a 2-month follow-up. RESULTS: The occurrence of EM among children with LNB was 37 out of 103 (36%). Gender, age, observed tick bite, clinical features, duration of neurological symptoms or clinical outcome did not differ significantly between LNB patients with or without EM. However, facial nerve palsy was significantly more common among children with EM in the head and neck area. CONCLUSION: EM occurred in 36% of children with LNB and the location on the head and neck was more common among children with facial nerve palsy. EM was not associated with other specific clinical characteristics or outcome. Thus, the occurrence of EM in children with LNB cannot be useful as a prognostic factor for clinical outcome. This aspect has not previously been highlighted but seems to be relevant for the paediatrician in a clinical setting.

Edema de Calabar en una niña guineana: loasis / Guinean child with Calabar swelling: Loiasis

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Symptom load and general function among patients with erythema migrans: a prospective study with a 1-year follow-up after antibiotic treatment in Norwegian general practice.

OBJECTIVE: Promptly treated erythema migrans (EM) has good prognosis. However, some patients report persistent symptoms. Do patients with EM have more symptoms than the general population? We describe individual symptoms and general function in EM-patients at time of diagnosis and one year after treatment. DESIGN: Prospective study with 1-year follow up after treatment. Questionnaires included a modified version of the Subjective Health Complaints Inventory, comprising three additional Lyme borreliosis (LB) related symptoms. General function was assessed using a five-point scale modified from the COOP/WONCA charts. SETTING: Norwegian general practice. SUBJECTS: A total of 188 patients were included in a randomized controlled trial comparing three antibiotic regimens for EM, of whom 139 had complete data for this study. MAIN OUTCOME MEASURES: Individual symptoms, symptom load and general function. RESULTS: Mild symptoms were common, reported by 84.9% at baseline and by 85.6% at follow-up. At baseline, patients reported a mean of 5.4 symptoms, compared with 6.2 after one year. Severely bothersome symptoms and severely impaired general function were rare. Tiredness was the most reported symptom both at baseline and at follow-up. Palsy (other than facial) was the least reported symptom, but the only one with a significant increase. However, this was not associated to the EM. CONCLUSION: The symptom load was comparable to that reported in the general population. We found an increase in symptom load at follow-up that did not significantly affect general function. IMPLICATION: Monitoring patients' symptom loads prior to treatment reduce the probability of attributing follow-up symptoms to LB. Key points Erythema migrans has a good prognosis.Patients treated for erythema migrans have a slight increase in symptom load one year after treatment. This increase does not affect general function. The levels of subjective health complaints in patients treated for erythema migrans are comparable to the background population.

Manifestaciones articulares en enfermos de Lyme / Articular manifestations in patients with Lyme disease

Objetivos. Determinar el porcentaje de pacientes con clínica articular entre los enfermos de Lyme en el NO de España y conocer su evolución y respuesta al tratamiento. Pacientes. Se realizó un estudio retrospectivo (2006-2013) revisando las historias clínicas de los enfermos de Lyme con clínica articular. Se analizaron las manifestaciones clínicas, los datos de laboratorio, el tratamiento y la evolución de los enfermos. Resultados. Diecisiete de 108 pacientes confirmados como enfermos de Lyme (15,7%) presentaban clínica articular. De estos 17, el 64,7% presentó artritis, el 29,4% artralgias y el 5,9% bursitis. La rodilla fue la articulación más afectada. La clínica articular se asoció frecuentemente a manifestaciones neurológicas, dermatológicas o cardíacas. La mayoría de los pacientes estaban en fase iii. El 11,8% evolucionó a artritis crónica recidivante, aunque recibieron tratamiento adecuado. Conclusiones. En zonas con elevado riesgo de picadura por garrapatas, la presencia de clínica articular debe hacernos sospechar la posibilidad de una enfermedad de Lyme con objeto de establecer de forma precoz un tratamiento adecuado que evite secuelas (AU)

Objectives. To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. Patients. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Results. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Conclusions. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels (AU)

Borrelial Lymphocytoma in Adult Patients.

BACKGROUND: Information on the course and outcome of borrelial lymphocytoma (BL) is limited. METHODS: The study comprised 144 adult patients (75 female, 69 male; median age, 49 years) who had BL diagnosed at a single center between 1986 and 2014 and were followed up for 1 year. RESULTS: BL was located on the breast in 106 patients (73.6%), on the ear lobe in 27 (18.8%), and elsewhere in 11 (7.6%). The median duration of BL before diagnosis was 27 days (interquartile range [IQR], 9-68 days). Concomitant erythema migrans was registered in 104 of 144 patients (72.2%); other objective manifestations of Lyme borreliosis (LB) were present in 11 (7.6%). Immunoglobulin M and/or G borrelial serum antibodies were present in 72 patients (50%). Borreliae were isolated from BL lesions in 14 of 42 patients (33.3%) who had not received antibiotics before skin biopsy. Of 13 typed Borrelia strains, 11 were B. afzelii, 1 was B. garinii, and 1 was B. bissettii The median duration of BL after starting antibiotic treatment was 21 days ([IQR], 10-30 days); the average duration was longer in patients who were older, had longer BL duration before treatment, or had signs of disseminated LB. Treatment failure occurred in 14 of 144 patients (9.7%). Patients with signs or symptoms of disseminated LB before treatment had nearly 4 times higher odds of treatment failure (95% confidence interval, 1.22-13.07) than those without such symptoms. All patients with treatment failure had uneventful outcome after retreatment. CONCLUSIONS: BL is a rare manifestation of early localized LB. Fourteen-day antibiotic treatment, as used for erythema migrans, is effective.

Erythema migrans associated with partial Horner's syndrome.

Lyme disease is a tick-borne illness caused mainly by three species of spirochaete Borrelia--B. burgdorferi, B. afzelii and B. garinii. It has three stages of presentation--early localised, early-disseminated and late Lyme. Erythema migrans is the most common manifestation of Lyme disease, and is usually seen 7-14 days after the tick bite. Patients seldom remember the tick bite. Patients may often present with neurological manifestations indicating neuroborreliosis. These manifestations range from a simple nerve palsy to severe complications such as papilloedema, myelitis or meningitis. We present a case of a 37-year-old woman who presented with partial Horner's syndrome, which was associated with erythema migrans, and other signs of Lyme disease.

Delayed onset of the Jarisch-Herxheimer reaction in doxycycline-treated disease: a case report and review of its histopathology and implications for pathogenesis.

The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.

Are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?

Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) are endemic in central part of Slovenia. We tested the hypothesis that patients with erythema migrans (EM) from this region, who have leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial phase of TBE but not in patients with LB) are coinfected with Anaplasma phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of concomitant HGA or the initial phase of TBE. Comparison of clinical and laboratory findings for 67 patients with EM who disclosed leukopenia/thrombocytopenia with the corresponding results in sex- and age-matched patients with EM and normal blood cell counts revealed no differences. In addition, patients with typical EM and leukopenia and/or thrombocytopenia tested negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well as for the presence of specific IgG antibodies to A. phagocytophilum antigens by IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0 to 5.3%) with typical EM (the presence of this skin lesion attests for early Lyme borreliosis and is the evidence for a recent tick bite) was found to be coinfected with A. phagocytophilum or had a recent primary infection with TBE virus. The findings in the present study indicate that in Slovenia, and probably in other European countries endemic for LB, TBE and HGA, patients with early LB are rarely coinfected with the other tick-transmitted agents.

Enfermedad de Lyme: a propósito de dos casos / Lyme disease: report of two cases

La borreliosis de Lyme es una enfermedad multiorgánica con afectación principalmente dermatológica, reumática, neurológica y cardiaca. La detección y el tratamiento en los primeros estadios son básicos para evitar su progresión. El pediatra, por tanto, debe conocer las manifestaciones clínicas de la enfermedad, así como establecer un correcto diagnóstico y tratamiento. Se exponen dos casos que incluyen las formas más frecuentes de presentación (AU)

Lyme borreliosis is a multisystem disease mainly dermatological, rheumatical, neurological and cardiological. The detection and treatment in the early stages are essential to prevent its progression. The pediatrician, therefore, must be aware of the clinical presentations of the disease as well as to establish a correct diagnosis and treatment. Two cases are presented involving the most common forms of presentation (AU)

Disseminated Lyme borreliosis preceded by hepatitis in an African American male.

Lyme disease is the most common tick-borne disease in the United States and has a multitude of systemic effects. Infrequently, however, Lyme disease is seen to cause liver dysfunction. Dermatologists should be aware that early, disseminated borreliosis can present with multiple erythema migrans plaques and hepatitis.