Continuing Education Activity
Cat scratch disease is an illness caused by an intracellular gram-negative rod known as Bartonella henselae. It affects the lymph nodes draining the area where a cat scratch or bite occurs, causing regional lymphadenopathy. This activity illustrates the evaluation and treatment of cat scratch disease and explains the role of the interprofessional team in managing patients with this condition.
Objectives:
Identify Bartonella henselae as the etiologic agent in cat scratch disease.
Describe the pathophysiology of cat scratch disease.
Review the use of antibiotics in mild to moderate disease and the disseminated form of cat scratch disease.
Explain the importance of collaboration and communication among the interprofessional team members to enhance the delivery of care for patients affected by cat scratch disease.
Introduction
Cat scratch disease (Cat scratch fever) causes a febrile illness with subacute regional lymphadenopathy. The agent of infection is Bartonella henselae. In most cases, there is a spontaneous resolution within 2 to 4 weeks. More severe and disseminated disease can occur in both immunocompetent and immunocompromised hosts. Cat scratch disease was initially described in the 1930s, and the association of the illness with cats was identified in the 1950s. Cat scratch should be considered in the differential diagnosis of any acute, subacute, or chronic lymphadenopathy.[1][2][3]
Etiology
The principal etiologic agent of catscratch diseaseisB. henselae- a fastidious intracellular gram-negative rod. The infection affects the lymph nodes draining the area of inoculation, usually from a scratch or bite of a young cat. There have been clinical descriptions of cat scratch disease for over 50 years, but the bacteriologic agent was not identified for decades. Dr. Douglas Wear, a pathologist, identified a new bacterium in the lymph nodes of cat scratch patients. This led to decades of research to identify the bacteriologicagent. Initially, there was cross-reactivity between Chlamydia and Bartonella species. After the development of electron microscopy, the Warthin Starry stain was used to detect black spots of the bacteria in affected lymph node specimens. The entity ofbacillary angiomatosis in theAIDS eraidentifiedWarthin-Starry positive bacteriain the early 1990s andwasfound to be the same agentasa controlgroup ofcatscratchpatients.[4][5][6]
Epidemiology
Cat scratch disease typically causes a mild illness in immunocompetent hosts. Fifty-five percent of cases are in children younger than 18 years of age; 60% of these are males. More than one-half occur in September through January in the United States. The distribution is worldwide.
The vector of cat scratch diseaseare cats that acquire the bacteria from the cat flea (Ctenocephalides felis) bite with subsequent bacteremia. The cat is not symptomaticat the time. B. henselae is difficult to culture but can be detected by serologic or by PCR methods. Infection may be acquired from scratch, bite, or infected saliva through broken skin. Fifty-six percentof cats with bacteremia are less than 1 year of age.[7]
Pathophysiology
The clinical hallmark is lymphadenopathy at the site of inoculation. In the immunocompetent host, a granulomatous response ensues. The immunocompromised host may develop a vascular-proliferative response. Affected lymph nodes become enlarged and tender over one to two weeks. Cat scratch diseaseis a common cause of chronic lymphadenopathy as well, which may spreadbeyond the site of inoculation. Cat scratch diseasecan disseminate to the eye, liver, spleen, and central nervous system (CNS).
Histopathology
Histological examination of the lymph nodes is characterized by granulomas, classically with microabscesses in the center of the lesion. Similar histologic changes may occur in the inoculation site as well as regional lymph nodes.
History and Physical
Eighty-five percent to 90% of children have self-limited lymphadenopathy accompanied by high fever. Patients with disseminated illness may have a spectrum of complications, especially in the veryyoung, elderly, and immunocompromised hosts such as transplant or patients with HIV. Involved systems may include the cutaneous, lymphatic, and visceral organs. More uncommonly, there may be ocular and neurologic involvement.
Cutaneous manifestations begin as an erythematous papule, vesicle, or nodule, which is known as the primary inoculation lesion. This lesion usually persists from one to three weeks but can last for months. The primary inoculation site may be a mucous membrane such as the conjunctiva that heals without scarring and is not detected. Examination of intertriginous areas, other skin creases as well as the scalp may help demonstrate the primary lesion.
Lymphatic system involvement presents as tenderlymphadenopathy, regional, and may be solitary or multiple nodes 1 to 5 cm in diameter. There is overlying erythema. Ten percent may suppurate. The lymph nodes are enlarged proximal to the inoculation site. Common sites are the axillary, epitrochlear, cervical, supraclavicular, or submandibularlymph nodes. The lymphadenopathy may last from 1 to 4 months.
Visceral organ involvement may include the liver, spleen, or both and present with fever, weight loss, and abdominal pain. There may be elevated acute phase reactants and liver function tests. Cat scratch disease may be the cause of up to one-third of children with fever of unknown origin.
Ophthalmic complications include neuroretinitis, papillitis, optic neuritis, and most commonly Parinaud Oculoglandular syndrome. This is an atypical presentation found in 2% to 8% percent of children, which involves an inoculation site in the conjunctiva. There is local adenopathy, typically preauricular, upper cervical, or submandibular, with severe conjunctival infection. The conjunctival infection resolves in several weeks, but the lymphadenopathy may persist for months. Cat scratch may also cause focal or multifocal retinochoroiditis, panuveitis, branch retinal artery, and vein occlusion, leading to retinal detachment.
Neurologic complications of cat scratch include ataxia, cranial nerve palsies, and a dementia-like picture in older patients. Children typically present with encephalitis or aseptic meningitis. However, status epilepticus has been reported.
A myriad of musculoskeletal complaints has been associated with cat scratch disease, including arthralgias, myalgias, and frank arthritis.
Evaluation
There may be a presumptive diagnosis of cat scratch disease, given the correct historical and examination findings. B. henselaeis difficult to culture. Exposure to cats is usually necessary for diagnosis. Serologic testing may confirm the diagnosis with EIA or IFA; however, negative serologic tests do not rule out the diagnosis. Lymph node biopsy is not indicated routinely but should be considered if the diagnosis is unclear. Historically, excision of affected lymph nodes has been avoided for fear of the development of fistulas. Ultrasound may aid needle aspiration to obtain tissue.[8][9]
Treatment / Management
In mild cases, treatment may not be necessary. Supportive care, including antipyretics and anti-inflammatory medications in addition to warm compresses to the inoculation site, may be all that is needed. In mild tomoderate presentation in immunocompetent patients, a course of azithromycin may be indicated.Azithromycin for 5 days has been shown to relieve the pain of severe lymphadenopathy but shown no reduction in the overall duration of symptoms. Azithromycin dose is 10 mg/kg day 1 and 5 mg/kg days 2 to 5. Individuals weighing greater than or equal to 45 kg can receive the adult (maximum) dose of 500 mg day one and 250 mg day 2 through 5. Immunocompromised patients should be treated to help prevent theprogression tosevere systemic disease. Antibiotic regimens includingrifampin,trimethoprim-sulfisoxazole, andciprofloxacinare available for severe, disseminated disease.[7][10][11]
Differential Diagnosis
Differential diagnoses include causes of acute, subacute, and chronic lymphadenopathy. The differential does include viral agents such as CMV, HIV, and EBV, but these agents usually cause diffuse lymphadenopathy. Skin papules similar to the lesion at the inoculation site may occur in fungal infections, leishmaniasis, and nocardiasis. In immunocompromised hosts, there may be a myriad of infectious agents to consider. The presentations of HIV as bacillary angiomatosis may be confused with Kaposi sarcoma.
Prognosis
In 90 to 95% of children, cat scratch disease will resolve spontaneously with symptomatic control, including analgesics, antipyretics, and warm compresses. In patients with disseminated disease, recovery may take months to a year with morbidities depending on the system involved. The immunocompromised host may have a debilitating course.
Pearls and Other Issues
Cat scratch disease is a common cause of lymphadenopathy, particularly in the pediatric population. A thorough history and physical examination, as well as a high index of suspicion, will aid in the diagnosis. The course may be benign or severe, and protracted. The age of the patient and comorbidities should be considered in the evaluation and treatment of the affected individual. Prevention of the disease requires adequate flea control and supervision of children around young cats.
Enhancing Healthcare Team Outcomes
Cat scratch disease is not uncommon in North America. The majority of patients present to the emergency department, and because of its varied presentation, the disorder is best diagnosed and managed by an interprofessional team that includes an infectious disease expert, neurologist, surgeon, ophthalmologist, and internist. The outcomes for immunocompetent patients with cat scratch disease are excellent. However, those who have involvement of the peripheral or central nervous system may develop some neurological deficit that may persist after treatment. Death in immunocompetent patients is rare. The lymphadenitisoften takes several months to resolve, but most patients develop lifelong immunity to the infection. The prognosis in patients who are immunocompromised is guarded.[12][13][Level 5]
References
- 1.
Shorbatli LA, Koranyi KI, Nahata MC. Effectiveness of antibiotic therapy in pediatric patients with cat scratch disease. Int J Clin Pharm. 2018 Dec;40(6):1458-1461. [PubMed: 30446895]
- 2.
Aguiar F, Martins-Rocha T, Rodrigues M, Brito I. Seronegative cat scratch disease in a patient with systemic lupus erythematosus. Acta Reumatol Port. 2018 Jul-Sep;43(3):241-242. [PubMed: 30414376]
- 3.
Canneti B, Cabo-López I, Puy-Núñez A, García García JC, Cores FJ, Trigo M, Suárez-Gil AP, Rodriguez-Regal A. Neurological presentations of Bartonella henselae infection. Neurol Sci. 2019 Feb;40(2):261-268. [PubMed: 30368695]
- 4.
Mabra D, Yeh S, Shantha JG. Ocular manifestations of bartonellosis. Curr Opin Ophthalmol. 2018 Nov;29(6):582-587. [PubMed: 30124532]
- 5.
Mantis J, Ali Y, Junejo SZ. Cat-Scratch Disease in an AIDS Patient Presenting with Generalized Lymphadenopathy: An Unusual Presentation with Delayed Diagnosis. Am J Case Rep. 2018 Aug 02;19:906-911. [PMC free article: PMC6083936] [PubMed: 30068900]
- 6.
Erdem G, Watson JR, Hunt WG, Young C, Tomatis Souverbielle C, Honegger JR, Cassady KA, Ilgenfritz M, Napolitano S, Koranyi K. Clinical and Radiologic Manifestations of Bone Infection in Children with Cat Scratch Disease. J Pediatr. 2018 Oct;201:274-280.e12. [PubMed: 30041935]
- 7.
Nelson CA, Moore AR, Perea AE, Mead PS. Cat scratch disease: U.S. clinicians' experience and knowledge. Zoonoses Public Health. 2018 Feb;65(1):67-73. [PubMed: 28707827]
- 8.
Jost M, Latz A, Ballhorn W, Kempf VAJ. Development of a Specific and Sensitive Enzyme-Linked Immunosorbent Assay as an In Vitro Diagnostic Tool for Detection of Bartonella henselae Antibodies in Human Serum. J Clin Microbiol. 2018 Dec;56(12) [PMC free article: PMC6258866] [PubMed: 30257897]
- 9.
Donà D, Nai Fovino L, Mozzo E, Cabrelle G, Bordin G, Lundin R, Giaquinto C, Zangardi T, Rampon O. Osteomyelitis in Cat-Scratch Disease: A Never-Ending Dilemma-A Case Report and Literature Review. Case Rep Pediatr. 2018;2018:1679306. [PMC free article: PMC5902065] [PubMed: 29808150]
- 10.
Pennisi MG, Marsilio F, Hartmann K, Lloret A, Addie D, Belák S, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hosie MJ, Lutz H, Möstl K, Radford AD, Thiry E, Truyen U, Horzinek MC. Bartonella species infection in cats: ABCD guidelines on prevention and management. J Feline Med Surg. 2013 Jul;15(7):563-9. [PubMed: 23813816]
- 11.
Niedzielska G, Kotowski M, Niedzielski A, Dybiec E, Wieczorek P. Cervical lymphadenopathy in children--incidence and diagnostic management. Int J Pediatr Otorhinolaryngol. 2007 Jan;71(1):51-6. [PubMed: 17097154]
- 12.
Barros S, de Andrade GC, Cavalcanti C, Nascimento H. Cat Scratch Disease: Not a Benign Condition. Ocul Immunol Inflamm. 2018;26(7):1115-1122. [PubMed: 28665750]
- 13.
Prutsky G, Domecq JP, Mori L, Bebko S, Matzumura M, Sabouni A, Shahrour A, Erwin PJ, Boyce TG, Montori VM, Malaga G, Murad MH. Treatment outcomes of human bartonellosis: a systematic review and meta-analysis. Int J Infect Dis. 2013 Oct;17(10):e811-9. [PubMed: 23602630]
Disclosure: Katherine Baranowski declares no relevant financial relationships with ineligible companies.
Disclosure: Ben Huang declares no relevant financial relationships with ineligible companies.