Vet FHT 2007 Oct 2008 Mar.Pdf (8.042Mb)

D ouble Issue O ctober 2 0 0 7 - M arch 2 0 0 8 Vol. 23, No. 1 health to

C linical D ecision M aking C l in ic a l D e c is io n

M a k in g Page 1 Professors Richard Malik,1,2 DVSc, DipVetAn, PhD, FACVSc, FASM, and Paul J. Canfield,2 DVSC, PhD, FACVSc, Grad Cert Higher Ed FRCPathi R e fr a c t o r y U lcer s o n t h e N asa l B r id g e ‘Post Graduate Foundation in Veterinary Science and “Faculty of Veterinary Science, University of o f a Y o u n g C a t : A n Sydney, Australia E x e r c is e in D ia g n o s t ic

R e a s o n in g ! 8 &Rlo2d4nifts)j An j which patients pres­ Page 6 Introduction and Conceptual Framework ent with signs that appear referable to N ontuberculous mandibular salivary gland disease, but Reasoning is a term used to refer to M ycobacterial generally respond completely to anticon­ S y n d r o m e s in C ats mental activity through which we vulsant drugs such as phenobarbitone. It Page 15 transform available information in order is therefore vital that we learn through to reach conclusions (in our case the our working life how to draw on the * Adapted with diagnosis of disease). It requires decision experience of junior colleagues (fresh out permission from the making (choosing between alternatives) of veterinary school), senior colleagues proceedings of the 19th j and problem solving (finding paths to annual Fred Scott (with vast experience, and special “local” desired goals - in our case determining Feline Symposium knowledge), textbooks, local and inter­ held at Cornell on July | plans to prove or disprove diagnostic national experts, and medical and veteri­ 27-29, 2007. possibilities or therapeutic approaches). nary electronic databases, and resources such as the Veterinary Information As veterinarians in small animal Network (VIN). practice, not a day goes by that we do not make critical decisions about the In relation to diagnosis, there are investigation and treatment of cases at least three important conceptual under our care. Interestingly, most of us approaches: have received very little specific training in clinical decision making as part of our 1. Pattern recognition — the recogni­ undergraduate curriculum, and most tion of characteristic combination of continuing education forums emphasize clues or signs (e.g., cutaneous reaction the acquisition of new knowledge, rather patterns, radiologic patterns, histologi­ than philosophical approaches to diag­ cal patterns, hematological patterns). nostic and therapeutic decision making. 2. Problem-based medicine In small animal medicine, we are 3. Diagnosis based on clinical prob­ frequently confronted with disease ability — i.e., that certain diseases conditions we have never encountered occur much more commonly than before. This makes life challenging and interesting, but it can also make life very others. stressful. We try our best to use common The best diagnosticians can use all sense, deductive reasoning, and to work of these approaches interchangeably, things out first from principles using a combining great analytic skill, a systematic pathophysiologic approach. Unfortu­ approach, but utilizing, also, good clinical nately, some things are counter-intuitive. intuition, which can make the diagnostic For example, the disease necrotizing process faster and less expensive. — ► continued on page 2 In this new century, veterinar­ 3. Skepticism — non-acceptance tongue was elevated by application ians more than ever should try to of findings until verified. In of pressure to the intermandibular consider a scientific approach to our case, don’t accept evidence space. The abdomen was palpated clinical decision making. The scien­ unless it has been well proven gently; however, no pain, discon tific approach or method is founded through testing. fort or abnormal structures were evident. on several key values or standards, 4. Accuracy — gathering and eval­ which are linked: uating information for accuracy. Questions for Consideration: In our case, it is evidence-based 1. Objectivity — evaluating the medicine. Rather than continue What is your Clinical Assessment? evidence free from bias as much to write abstractly about these (This is easy.) as is humanly possible; bias disparate concepts, I will attempt 1. The cat may or may not have develops from our past experi­ to illustrate them by working swallowed a sewing needle. ences. through what would seem to be 2. The needle may or may not have 2. Open-mindedness — a commit­ a “very straight forward” case. had attached thread. ment to changing one’s views in I will then challenge readers in 3. If so, there may be as a conse­ the face of evidence that these relation to HOW and WHY they quence a variety of clinical views are inaccurate. make clinical decisions. problems. Case Presentation What are the potential problems? Signalment 1. Penetration of the pharynx. ^£U N E hea£ ^ The ultimate Magic is a two-year-old desexed purpose of the 2. Penetration of the esophagus. female Australian mist cat. This Cornell Feline 3. Migration of the needle from u| Health Center is an Australian breed, based on the stomach to other sites. ■ M is to improve initial crosses between Burmese (50 a. W hich sites? the health of percent), Abyssinian (25 percent) cats everywhere and Australian domestic crossbred b. W hy these sites? by developing methods to prevent cats. or cure feline diseases, and by 4. Complications related to three providing continuing education to — i.e., intestinal plication. Presenting Complaint veterinarians and cat owners. All a. When does plication occur? The cat may have ingested a contributions are tax-deductible. sewing needle. What would you do next? Interim Director: (This is a bit harder.) Fred W. Scott DVM, PhD History 1. Radiology Veterinary Consultants: The owner observed the cat play­ 2. CT Christine Bellezza, DVM ing with a sewing needle. The needle Marnie FitzMaurice, DVM allegedly had no thread attached. The 3. MRI Paul Maza, DVM owner tried to intervene and stop 4. Endoscopy Carolyn McDaniel, VMD the cat from playing with the needle; Administrator: 5. Hematology, biochemistry and however, when the owner caught the urinalysis, plus FIV and FeLV Michael Lenetsky cat, there was no needle to be found. Administrative Assistants: tests To complicate matters further, the Kathleen Mospan cat then ate 100 grams (6.25 oz.) of Radiology Donald Personius 1. Chest? Pamela Sackett commercial tinned cat food. Sheryl Thomas 2. Abdomen? Physical Findings Phone: (607) 253-3414 No abnormalities were detected 3. Whole cat, in one go? Consultation: 1-800-KITTYDR on physical examination. Coughing Web: www.vet.cornell.edu/FHC 4. How many views? was not noted, nor was vomiting ©2008 by Cornell University on or regurgitation during the dura­ behalf of the Cornell Feline Health Center, College of Veterinary Medi­ tion of the physical examination. cine, Ithaca, NY 14853. No foreign bodies or lesions were All rights reserved. Permission to reprint se­ detected within the oral cavity. A lected portions must he obtained in writing. thread was not evident in the vicin­ Cornell University os am equal opportunity, affirmative action educator and employer. ity of the lingual frenulum when the \ ______s

-2- Questions: (1) Where is the needle? (2) Do we need a 2nd radiograph?

CRITICAL QUESTIONS • How should we manage this case? • On what basis should we make decisions regarding clinical management?

Lateral radiograph of Magic

How do we manage this patient? Is endoscopic removal a viable the United Kingdom (U.K.). He (This may be controversial.) possibility? had seen them migrate to the 1. Conservative - do nothing. 1. In general, yes - although liver or thoracic cavity. needles are hard to catch and 2. Conservative - use drugs, other 2. Veterinary Information Network hard to safely retrieve. techniques. (VIN) — A U.K. surgeon recom ­ 2. You need good equipment and mended surgery to be sure 3. Endoscopic removal. great expertise. the cat would be okay. He said 4. Surgical removal. the needle might pass without 3. In this case, the ingestion of surgery, but he couldn’t be sure On what basis should we make deci­ food immediately prior to this would happen. sions regarding clinical manage­ presentation would have made ment? endoscopic removal very prob­ Veterinary textbooks 1. Look up in textbooks. lematic. Furthermore, anesthe­ A wide variety of textbooks were . Ask colleagues. sia would be contraindicated in consulted, but they did not prove this setting. helpful in this case. 3. Ask local experts/specialists. 4. Consult veterinary and medi­ What about surgery? Evidence-Based Medicine using cal databases - CAB, Medline, Advantages Electronic Databases PubMed. 1. It likely will resolve the problem. 1. Look at veterinary databases, which are most reliable. 5. Post a question on VIN. 2. It has a high success rate. 2. Also, look at medical databases. But before we do that, what are 3. There should be minimum These are less reliable, but more the unique considerations of the morbidity involved. inform ation is available for present case? 4. It makes more money for the certain topics, such as those 1. The cat has been presented early. clinic. pertaining to this case. 2. We cannot be sure whether or 5. It takes away all the possible 3. Case series are much more help­ not there is thread attached to complications associated with a ful than individual case reports the needle. penetrating object and thread. when looking for overall recom­ 3. The cat has just eaten a large Disadvantages mendations. meal. 1. It is invasive. 4. Look at: (i) year of the report, 4. It is a young, healthy patient that 2. It costs the owner more money. (ii) the country of origin, and should cope okay with anesthesia (iii) the institution. These are and surgery, if they are done in 3. There will be some pain and very germane to the quality and an appropriate manner. morbidity for the patient. applicability of the data. 5. Money is not an issue with these Ask learned colleagues 5. Textbooks are also useful, but owners. 1. Dr. Dick Churcher (Australian generally they are rated low internist) strongly recommend­ j. There is time to think and down in the list compared to ed surgery based on his experi­ research the best course of original peer-reviewed papers. ence with migrating needles in action.

-3- Veterinary Database (CAB) In this instance, the search was technically difficult since you needed some patience to find the correct key words (stomach, cat, needle). Only limited information was available, consisting of only two case series.

1. Gunsser (1978). Sewing needles and fish hooks as foreign bodies in dogs and cats. Diagnosis and therapy. In this report of 57 dogs and 15 cats, six of the nine cats with gastric needles passed the needles spontaneously in three to four days. 2. Felts et al. (1984). Thread and sewing needles as GI foreign Intestinal plication from a string foreign body in a cat bodies in the cat: a review of 64 cases. In this report from the Animal Medical Center in New York City, m ost cases had thread 2. Most published reports talk were watching for and anticipat­ and required surgery. about foreign bodies generically ing signs of early peritonitis, Enough information is available rather than just sewing needles. pancreatitis, ileus, partial intes­ tinal obstruction, etc. to give you an impression that 3. Some case series have as many both good and bad outcomes were as 18,200 cases! 3. The cat was fed judiciously thn possible, but there is insufficient times daily with small meals of a 4. Gun et al. (2003) reported on quality data to be definitive in commercial tinned cat food that 49 cases of safety pin inges­ recommending treatment strate­ was finely mashed up using a tion in which 41 percent were gies. Interestingly, young cats were fork. passed spontaneously, while over represented, and the presence the remaining cases required 4. Another radiograph was taken of thread must be suspected in all endoscopy or surgery. the following morning. The cases as it is the incentive for curi­ needle was not within the intes­ osity and play. 5. In reviewing many of the case tinal tract. series available, it is apparent What about individual case that: the majority of foreign 5. The cat had a good appetite for reports (like this one)7. bodies that reach the stomach tasty food while she was in the 1. They tend to be written to continue to pass through hospital. highlight unusual or dramatic without sequelae; prokinetic 6. The cat’s tem perature was sequelae, e.g., Hunt et al. (1991) drugs are not helpful; common marginally elevated during the reported on the suspected sites of trouble are the pylorus, first 36 hours. cranial migration of two sewing duodenal flexure, and ileoceco- 7. No feces were passed for three needles from the stomach of a colic valve; and pins are rarely days. dog into the heart. a problem because of Jackson’s 2. They tend not to report simple, axiom, i.e., the blunt weighted 8. The cat was given amoxicillin happy, unchallenging outcomes. end passes first. (100 mg orally twice daily) during hospitalization. How did we manage our patient? What about human medical data­ 1. We hospitalized the patient. 9. She was also given some Coloxyl bases (Medline or Pub Med ft (50 mg orally) every 12 hour- 1. An enormous number of cases 2. We monitored rectal tempera­ from day three on. have been reported as case reports, ture, demeanor and appetite case series, or large case series. every eight to 12 hours. We A milestone occurred on day four when the needle was passed 1. The needle was attached to a segment of stool. 2. The needle measured 3.8 cm in length. 3. It had a cotton thread attached, folded in two. The thread measured 74 cm. 4. Presumably, the stool pulled the needle and thread through the rectum.

Further Reading

Veterinary references 1. Gunsser I. Sewing needles and fish hooks as foreign bodies in dogs and cats. Diagnosis and therapy. [German] Berliner undMunchener Tierarztliche Wochenschrift. 91:399-403,1978. 2. Felts JF, Fox PR, Burk RL. Thread and sewing needles as gastrointestinal foreign bodies in the cat: a review of 64 cases. J A m Vet M e d A sso c 184: 56-59,1984. 3. H unt GB, Bellenger CR, Allan GS, Malik R. Suspected cranial m igration of two sewing needles from the stomach of a dog. V e tR e c 128:329-330,1991.

Human references 1. Arana A, Hauser B, Hachimi-Idrissi S, Vandenplas Y. Management of ingested foreign bodies in childhood and review of the literature. E u r J Pediatr. 160(8):468-72, 2001. 2. Berggreen PJ, Harrison E, Snaowski RA, et al. Techniques and complications of esophageal foreign body extraction in children and adults. Gastrointest Endosc. 39:626-630,1993. 3. Campbell JB, Condon VR. Catheter removal of blunt esophageal foreign bodies in children. Survey of the Society for Pediatric Radiology. Pediatr Radiol. 19:361-365,1989. 4. Cheng W, Tam PK. Foreign body ingestion in children: experience with 1,265 cases./ Pediatr Surg. 34:1472-1476,1999.

5. Gun F, Salman T, Abbasoglu L, C’elik R, Qelik A. Safety-pin ingestion in children: a cultural fact. Pediatr Surg Internal 19:482-484, 2003.

6. Litovitz TL, Klein-Schwartz W, W hite S, et al. 1999 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am ] Emerg Med. 18:517-574, 2000. 7. M acpherson RI, Hill JG, Othersen HB, et al. Esophageal foreign bodies in children: diagnosis, treatment, and complications. Am J Roentgenol. 166:919-924,1996. 8. M cDermott VG, Taylor T, Wyatt IP, et al. Orogastric magnet removal of ingested disc batteries. / Pediatr Surg. 30:29-32,1995.

9. Panieri E, Bass DH. The management of ingested foreign bodies in children—a review of 663 cases. E u r J Em erg M ed. 2:83-87, 1995.

10. Schwartz GF, Polsky HS. Ingested foreign bodies of the gastrointestinal tract. A m Surg. 42:236-238, 1976.

11. Wahbeh G, Wyllie R, and Kay M. Foreign body ingestion in infants and children. Clin Pediatr. 41:633-640,2002.

-5- Refractory Ulcers on the Nasal Bridge of a Young Cat: An Exercise in Diagnostic Reasoning Professors Richard Malik,1,2 DVSc, DipVetAn, PhD, FACVSc, FASM, and Paul J. Canfield,2 DVSC, PhD, FACVSc, Grad Cert Higher Ed FRCPath

‘Post Graduate Foundation in Veterinary Science and “Faculty of Veterinary Science, University of Sydney, Australia

Case Study Questions: Presenting Complaint and (1) What is your clinical History: assessment? An eight-month-old castrated male (2) How would you investigate domestic crossbred cat is presented this case further? for multiple non-healing ulcers on the bridge of its nose.

Physical Findings: The lesions do not appear to be pruritic. There are no lesions like this on the nasal planum or on the digital pads. There is no suppura­ tion from the lesions. There are no When we trained as clinicians in a patient with sudden collapse current signs of nasal cavity disease veterinary school, the major focus and pale mucous membranes, the such as sneezing or nasal discharge. was on providing an overview of student palpates the abdomen whil^ The cat is constitutionally well. the many disease conditions that waiting for a finding to strike hin The lesions did not respond to a can affect the various body systems on the other hand, the expert clini­ four-week course of cephalexin, in disparate animal species. This cian is on a focused search mission, and have persisted while the cat was underpinned by “Problem- e.g., is there a palpable abdominal has been boarding in the clinic for orientated medicine,” a conceptual mass (spleen?) which may be seven days. approach which was has been well hemorrhaging into the peritoneal accepted in veterinary medicine space. Negative findings are often Background Concepts to be since the 1970s, and is taught in just as important as positive find­ Explored most veterinary colleges in North ings. America and Australia. Reasoning Problem Lists Let us start with some key defini­ It should be borne in mind that In problem-orientated medicine, tions. Reasoning refers to mental one of the factors that make teach­ presenting complaints, clinical activity through which we trans­ ing diagnostic reasoning so tricky signs, abnormal physical findings form available information in order is that expert clinicians do not and laboratory test results, infor­ to reach conclusions. In this specific follow a fixed pattern of patient mation from imaging modalities instance (clinical reasoning), we examination and evaluation. From and so forth can all be entered as refer to the integration of historical, the outset, they are generating, “Problems” in a Problem List. This physical, laboratory and imaging refining, and discarding diagnostic Problem List forms the cornerstone findings in order to make a diag­ hypotheses. The questions they of the patients medical record. nosis. It requires decision making ask in the history are driven by the These problems are then resolved, (choosing between alternatives) and hypotheses they are working with if possible, into a smaller number of problem solving (finding paths to “in the moment.” Even the physical entities which reflect the key under­ desired goals) - in this case, deter­ examination is somewhat driven lying disease processes giving rise t r mining plans to prove, or disprove, by specific key potential findings, the patients signs. The advantage c the diagnostic possibilities and/or rather than a pre-ordained check­ this approach is that it can be applied approaches to therapy. list. For example, when evaluating to any disease, simple or complex,

-6- and it works (or should work) even problem. Indeed, the presence of heuristic, where the clinician weighs for disease conditions that the clini­ multiple concurrent diseases is an the probability that the patients cian has never seen before, or not underrated problem when dealing key clinical features match those of wen heard about! The trouble with with complex cases, especially when patients with the leading diagnostic this system is that it is cumbersome, matters are further complicated by hypothesis under consideration. For tedious for simple cases, expensive preliminary treatments that have example, a cat with sudden onset and not well suited to the majority of been given by other veterinarians. of oculonasal discharge, sneezing, software systems used in veterinary This is why veterinary medicine can conjunctivitis, tracheal hypersensi­ practice. It is very useful, however, be so challenging. Unfortunately tivity and fever but no mouth ulcers in developing a conceptual frame­ this has resulted in “throwing out is most likely to have a viral upper work to explain to undergraduates the baby with the bathwater,” respiratory infection, with feline the logic that underpins analytic because an intuitive, thoughtful herpesvirus the most likely specific diagnostic reasoning. It should clinician can harness both pattern etiological agent. The clinician using form the cornerstone for clinical recognition AND analytic diagnos­ the representative heuristic can decision making when combined tic reasoning to sort out challenging reach erroneous conclusions if they with information from textbooks internal medicine cases. fail to consider the underlying prev­ and electronic databases. alence of two (or more) conflicting The novice veterinary practi­ diagnoses. For example, in a cattery tioner typically uses a “shot gun” with a history of chlamydiosis and approach to diagnostic testing, a solid vaccination program against hoping to hit a target without really viral respiratory pathogens, Chla­ knowing what that target is. The mydophila felis infection may be a increasingly accepted concept of more likely etiology than herpes­ a minimum data base - consist­ virus in this particular scenario. ing of a complete blood count, In either case, specific testing with a biochemical panel, urinalysis, a “gold standard” test, e.g., multi­ chest and abdominal radiographs plex PCR using an appropriately herlock Holmes - a great believer in and abdominal ultrasound - is the collected oropharyngeal swab is problem based analysis. Dr Watson can current expression of this approach, required to confirm the presump­ be seen suffering from passive smoking although it has merit in complex on the right. tive diagnosis. Mistakes also occur cases or in situations where there is when considering a pattern based no limit to the cost of the “work up.” Experienced clinicians, if they are on too small a number of observa­ The expert diagnostician, on the honest, will admit that much of the tions. In veterinary medicine, breed other hand, usually has one or two tim e they can recognize the cause of often plays an important role in specific targets in mind, and effi­ many patients’ problems by utilizing recognizing patterns of disease, e.g., ciently adjusts the testing strategy mental “short-cuts,” usually charac­ muscular dystrophy in Devon Rex with this in mind. Uncertainty in teristic patterns of historical clues, cats, and polycystic kidney disease veterinary m edicine is com pounded clinical signs and physical findings. in Persian cats. by the information overload that Such “pattern recognition” has been characterizes the modern world in A second commonly used frowned upon by some influential which we live. It has been said that a cognitive shortcut, the availability veterinary educationalists. This is good human internist needs at least heuristic, involves judgments made illogical, as in my experience the two million bits of information to of the ease with which similar best human and veterinary internists practice medicine. In order to cope, cases, including ones with unusual have the most sophisticated pattern most good clinicians use cognitive patterns or outcomes, can be recognition skills! The reason why shortcuts, or heuristics, to organize brought to mind. Clearly, vast clini­ this intuitive style of diagnostic complex unstructured material cal experience helps here, and so reasoning is so disdained is that from the clinical evaluation into a does a retentive memory. It is possi­ it may let you down if not utilized ble also to harness the corporate with checks and balances. This is manageable format. memory of the practice when using because some patients do not have H euristics this heuristic; for example, a type he “classic pattern,” while other Psychologists have found that of envenomation commonly seen patients with “a classic pattern” can people rely on three basic types of in that area, or a poisonous plant have a completely different disease, heuristics. Pattern recognition is seen in a particular location. Errors or a concurrent significant other an example of the representative -7- with this heuristic can be related breed associations can provide can suggest the diagnostic of allergic to recall bias, e.g., where bizarre the wrong anchor, e.g., making a rhinitis secondary to food allergy. diagnoses or catastrophic outcomes diagnosis of arrhythmogenic right This presumptive diagnosis can be are recalled with clarity, and force ventricular cardiomyopathy (boxer confirmed inexpensively by remov the judgments out of proportion to cardiomyopathy) in a boxer dog ing this food supplement from the their true value. For example, we are with incessant tachycardia, when diet, observation, and possibly, much more likely to recall the intes­ the dog instead has a re-entrant subsequent provocative exposure. tinal foreign body that “got stuck” junctional tachycardia. Another pertinent example would and caused an obstruction, rather be the sudden development of Cognitive scientists studying the than the many other cases which multifocal intracranial signs in thought processes of expert clini­ passed without noticeable adverse a young adult dog. The detailed cians have observed that internists sequelae. Obviously, recent experi­ neurological examination suggests group data into packets or “chunks”, ence is easier to recall and therefore multifocal central nervous system which are stored in their memories more influential with this heuristic disease (differential diagnosis and manipulated to generate diag­ in relation to clinical judgments. granulomatous meningoencepha­ nostic hypotheses. Because short­ litis, cerebral cryptococcosis, etc.), The third commonly used term memory typically holds seven which is usually investigated by cognitive shortcut, the anchor­ to ten items at a time, the number cross sectional imaging of the brain, ing heuristic, involves estimating of chunks of information that can cerebrospinal fluid (CSF) analysis probability by starting from a given be actively integrated into hypoth­ and serological testing. However, point (the anchor) and adjust­ esis generating activity is likewise the observation that the owners ing to the new case from there. limited. The cognitive shortcuts are young, university students with Although this can be a powerful listed above play a critical role in unusual dress sense and multiple tool, using the wrong anchor can generating diagnostic possibilities, piercings, suggests further history be very misleading, whereas using many of which are discarded as taking (Have you noticed any the correct anchor can be of great rapidly as they are formed. hash cookies missing from your benefit. For example, a colleague Linear and Non-Linear Logic stash?), observation in hospita' asks you to evaluate a Dachshund and a urinary toxicology screen M ost of the time, linear logic is used with posterior paralysis that is may be more prudent, less invasive in conducting clinical investiga­ thought, most likely, to be referable and more cost effective than a full tions. For example, the investiga­ to intervertebral disc prolapse. You neurological work-up! tion of a canine patient with nasal conduct a detailed neurological discharge would typically involve examination and are puzzled by the Counterintuitive Diagnoses examining the area (observation, presence of lower motor neuron Finally, it must be acknowledged palpation, percussion), diagnos­ signs in the hindquarters (hypo­ that in some instances certain clini­ tic imaging (radiographs, cross tonia, reduced tendon jerks and cal entities are so bizarre that their sectional imaging [computed withdrawal responses), and have diagnosis is almost counterintuitive, tomography (CT) or magnetic reso­ not had the opportunity of taking a and instead relies on recognizing nance imaging (MRI)], anterior and history in which the owners report a particularly arcane pattern of posterior rhinoscopy and obtain­ that the dog’s bark is altered, that it clinical findings. For example, the ing appropriate tissue specimens had been regurgitating and that the entity referred to as necrotizing sial- (washings, pinch biopsies) for owners had removed an Ixodes tick adenoadenitis refers to a condition laboratory investigations (cytol­ 24 hours prior to the development in which there is painful enlarge­ ogy, culture, histology, polymerase of posterior paralysis! No wonder ment of one or more mandibular chain reaction testing). Nine times you are confused - you have started salivary glands, associated with out of 10, this provides the correct from an erroneous reference point dysphagia, drooling of saliva and diagnosis, but often at the cost of a - the dog has “classical” tick paraly­ even infarction of the salivary gland very expensive and invasive investi­ sis, not a disc prolapse! Anomalous parenchyma. A logical diagnostic gation. Sometimes non-linear logic laboratory results often cause approach would involve inspection (i.e., lateral thinking) can produce anchoring heuristic headaches, of the affected glands and their a stunningly correct diagnosis. For e.g., the finding of an allegedly ducts, imaging of the glands, biops’ example, finding that the nasal elevated thyroxin value in a cat with or even surgical removal of the discharge developed one week after no goiter and normal history and glands. However, all these measures starting a peanut supplement to the physical examination! Sometimes prove to be unhelpful, and empiric diet in preparation for a dog show

-8- discovery of the effectiveness of certain anticonvulsants has led to This cat has stiffness and unyielding rigidity of one thoracic limb. The cat the proposal that this condition is is otherwise well. There may be clues tctually a form of “limbic epilepsy”. in the history that help establish the The recently described oropharyn­ diagnosis. geal pain syndrome of Burmese cats and phenobarbitone-responsive gas- troparesis and vomiting are other WHAT ARE THE CLUES? pertinent examples. Another entity WHAT IS YOUR DIAGNOSIS? in this category is sudden acquired retinal degeneration - a disease in which dogs suddenly develop peripheral blindness (bilaterally dilated pupils that fail to respond to “racing form guide approach” to corporate memory can be helpful! light) associated with Cushingoid diagnosis. This can be summed Another im portant them e is that the physical findings; the diagnosis is up by the expression “common patterns can be completely different made by exclusion by detecting things occur commonly”. Thus, in different species; for small animal a normal fundoscopic examina­ when confronted by a characteristic clinicians this is of key importance tion (initially) with an absent combination of clinical findings, or because diseases in cats and dogs electroretinal electrical response an anatomic diagnosis, then, based present in different ways, and occur (ERG) to a flash stimulus. It is only on chance, certain diseases are much with different frequencies. Hence, possible to immediately recognize more likely to be encountered than the commonly voiced viewpoint these rare, bizarre entities through others, at least in given geographical that “cats are not small dogs”. This expert knowledge, intuitive leaps, or regions. For example, it is possible is more of a problem for people therapeutic trials (if you are the first to say that of the many potential whose thinking style is less reliant person to encounter such an entity). causes of polydipsia/polyuria in on a problem-based approach. However, the use of electronic data- dogs, most patients in a general aases, Boolean logic, and sophis­ Clinical Intuition practice setting will have diabetes ticated key word searches using Another consideration, that almost mellitus, hyperadrenocorticism or search engines such as Google™ no one mentions, is that certain renal insufficiency (The exact order and Google Scholar™ can often be individuals make intuitive clini­ may vary from country to country, very helpful in finding informa­ cians. The current television series, or region to region because of differ­ tion on such diagnostic oddities. “House,” concerning a taciturn but ences in the gene pool and environ­ The process of clinical reasoning brilliant internist (Gregory House mental factors such as feeding and revolves around generating test­ MD played by the English actor day length in different geographical able hypotheses. These should be Hugh Laurie) is based on this prem­ regions). Other diseases, such as confirmed with further test(s), or ise. Probably such individuals would diabetes insipidus, are much less response to therapy, but if the test have made good criminal investiga­ likely to be encountered. results or therapeutic response is not tors, as there is without doubt an supportive, hypotheses need to be The trouble with “pattern recog­ art as well as a science in diagnostic discarded or substantially modified. nition” and “probability” is that you reasoning. Interestingly, the char­ must either have a lot of experience acter, Gregory House, was based in Unfortunately, the generation and (preferably including time spent part on Sherlock Holmes, hence the evaluation of appropriate diagnostic working alongside senior expert pun on the word House/Ho(l)me(s). possibilities is a skill not all clini­ clinicians), or you must do a lot of I have no doubt that detective Robert cians posses to the same degree, and rote learning, to make these diag­ Goren (from Law and Order Crimi­ this is likely a consequence of the nostic considerations work for you. nal Intent) would have also made an fact that people intrinsically think Local knowledge and the counsel of outstanding veterinary internist, as in different ways! a senior colleague can be very help­ he would have been a sophisticated Probability ful in this setting, which is unhelp­ exponent of pattern recognition, \ further critical component of ful for new graduates or locums, problem-orientated medicine, and diagnostic reasoning relates to and sometimes a good veterinary also, clinical intuition. probability theory, or if you will, a nurse/technician with a long

-9- Guidelines for Consideration This cat has multifocal lesions on Whatever way you like to approach the nasal bridge region. They have the diagnosis of disease, be aware: failed to response to antibiotics and corticosteroids. • Of the strengths and limita­ tions of each type of diagnostic WHAT IS YOUR DIAGNOSIS? approach • That jumping to a conclusion is natural, but may be harmful - always ask yourself “What 2. Detect and describe physical, Diagnostic Reasoning evidence am I basing this on?,” laboratory and imaging find­ This talk will flesh out some of these and question the veracity of the ings. Include useful “patterns”. issues by proving that we all use a evidence. If in doubt, do another combination of problem solving, more definitive test to confirm 3. Consider the pathophysiologic pattern recognition, clinical intu­ your first impression. basis for the observed findings. ition, and probability to work out An approach that considers • That your previous experiences what is wrong with our patients. the underlying physiological can mislead you in some cases derangements is most useful in Importantly, we will try to (i.e., keep an open mind). planning pharmacological and convince you that there is noth­ • Of accepting evidence too readi­ other interventions. ing wrong with developing your ly, just because it fits in with your own clinical style, which takes into 4. What conclusions can you bias or others’ views - always ask account: (i) the way you learn, (ii) draw, i.e., define a problem or yourself “how” and “why” about the way you “think,” (iii) whether problems. Try and move from evidence, i.e., maintain objectiv­ or not you have a certain type of the general to the specific, but ity and “healthy skepticism.” retentive memory (or not), and (iv) try to move further toward the whether you have reliable clinical • That your emotions and the way specific as you get additional intuition. you like to think and operate can information such as laboratory sometimes adversely affect your and imaging data. We will also try to demonstrate capacity to reach decisions and that there are many patterns; 5. How can you obtain the solve problems - know yourself! including imaging patterns (e.g., evidence to support your air bronchogram, alveolar pattern), • Remember that a single key conclusions (i.e., what is your dermatological patterns (“cutaneous finding can confirm or refute a plan for further investigation)? presumptive diagnosis. reaction patterns”), hematological 6. Are there implications for ongo­ patterns (e.g., stress leukogram We believe it is healthy to try to ing management, while you response), clinical chemistry cultivate a stereotyped approach to investigate further? patterns (e.g., high ALT with hyper­ the diagnostic process by answer­ 7. Consider using textbooks and thyroidism, increased ALP without ing the following questions: electronic databases using key jaundice in Cushings disease), 1. What can you deduce from the word searches to help in difficult cytological patterns (e.g., capsulated signalment, history, clinical cases. Do not be afraid to ask yeast with narrow necked budding signs and physical findings: your colleagues (senior and with cryptococcosis) - and that junior) for their opinions, but do there is nothing wrong with using • The time course of the disease not necessarily let them take over all of them. process? - construct a time/sign your own clinical reasoning. diagram • Which organ system(s) are affected? • What pathological process(es) are likely involved? Bobby Goren - a great exponent of • Is a pattern emerging? - does Problem-based medicine and pattern recognition it fit all the facts? Can YOU be a vetective?

-10- For example, we are all comfort­ This dog presented for masticatory muscle atrophy, able that the combination of absence of blink reflex (ipsilateral) but normal menace dysuria, hematuria, pollakiuria and reflex and dazzle response. tranguria are together suggestive of lower urinary tract disease; once we What is your pattern recognition diagnosis? have m ade this connection, it is easy What is your problem-based diagnosis? to sort out the specific diagnosis (infection, stones, neoplasia, etc). Likewise, we are comfortable about recognizing clinical syndromes. Clinical syndromes are really just species and Sporothrix schenckii have patterns; e.g., Horners syndrome ing is that infections affecting this been reported to produce similar (ptosis, miosis, third eyelid anatomic region develop through lesions by others. Conceptually prolapse) is a sophisticated pattern two different mechanisms. similar mycobacterial infections or that tells us something is interfer­ mycotic lesions can develop on the ing with sympathetic innervation Cases with Infection of the cornea following cat scratch abra­ of the eyeball; we then just need Naso-Ocular Region but without sions. The biologic behavior of these to remember the corresponding Concurrent Nasal Signs infections depends on the virulence neuroanatomic pathway to work out These cases likely result from of the pathogen, the initial dose of the complete differential diagnosis contaminated cat-scratch injuries. organisms inoculated, the subse­ (T1-T3 spinal cord disease, brachial Presumably the claw(s) of the feline quent host response, the effect of plexus disease, cervical disease and perpetrator are contaminated by subsequent medical and surgical middle ear disease). The presence viable, potentially-pathogenic, sap­ interventions and the chronicity of of Horner s syndrome with concur­ rophytic organisms. These are inoc­ the lesion. rent ipsilateral facial nerve paralysis ulated in such large numbers that non-specific defense mechanisms is an even more complex pattern, Although the precise loca­ (bleeding, inflammation, neutro­ and strongly suggestive of middle tion and appearance of lesions is philic phagocytosis, lysozyme) of ar disease. But you still need quite variable from case to case, the victim are overwhelmed. This diagnostics to work out whether the the relatively consistent anatomic results in a localized, variably inva­ problem is infectious, polypoid or distribution of lesions which will be sive infection of an otherwise immu­ neoplastic in origin. apparent from this presentation is nocompetent host. A wide range of strongly suggestive of a cat-scratch- The importance of using all tech­ microorganisms can be cultured etiology. One differential diagnosis niques will be emphasized in the from such cases including a vari­ for florid disease at this anatomic accompanying presentation. Many ety of bacteria and fungi normally site is insect-bite hypersensitiv­ clinical examples will be used. This residing in soil, rotting vegetation, ity. However, the punctate nature will include some com m on and well humus or dirt. Lesions are typically of the primary lesions, frequent recognized patterns, some more on the bridge of the nose, but they concurrent involvement of the ears arcane patterns, and also cases may also occur more laterally or and toes, and characteristic eosino­ where pattern recognition must be involve the nasal planum. philic histology distinguishes the tempered by a problem orientated underlying allergic basis. A further approach. In our referral centre in eastern Australia, opportunistic pathogens important diagnostic possibility is ulcerative dermatitis due to feline Differential Diagnosis of Diseases isolated from such cases (a total of herpesvirus type-1, which is asso­ Affecting the Nasal Bridge of Cats seven cats between 1987 and 2003) ciated with eosinophilic inflam­ Infections affecting the skin and have comprised the bacteria Cory- mation, mild concurrent upper subcutis of the naso-ocular region nebacterium pseudotuberculosis respiratory signs and in some cases are seen from time to time in feline (1 case), Mycobacterium avium (1 characteristic viral inclusion bodies practice. We have investigated in case) and Nocardia nova (1 case), in biopsy specimens; definitive diag­ excess of 20 of these cases since and the fungi Cryptococcus neofor- nosis depends on amplification of 1987 and the likely pathogenesis of mans (1 case), Exophiala jeanselmei herpesvirus amplicons using PCR, .nese infections has become appar­ (2 cases) and Paecilomyces lilacinus ideally on fresh tissue specimens. ent over the years. The key find­ (1 case). Mycobacterium avium, Exophiala jeanselmei, Alternaria This infection may respond to topi­

-11- cal agents used to treat cold sores in the protection of a longer hair coat. Many authorities would also people, or the systemic anti-herpes Finally, growth of many saprophytic recommend obtaining a minimum agent famciclovir. A recent paper species may be favored at the lower database consisting of a complete has shown the usefulness of intra- temperatures encountered at this blood count, serum biochemistr lesional interferon-omega in the anatomic prominence. It must be profile, urinalysis and possibly management of a refractory case. emphasized, however, that lesions tests for feline immunodeficiency Presumably the location of ulcer­ attributable to a similar range of virus (FIV) and feline leukemia ative lesions in these cases is related pathogenic saprophytes can develop virus before embarking on therapy. to the habit of cats to clean their on the body wall or distal extremi­ Concurrent metabolic problems noses of exudates by grooming via ties following contamination by such as renal insufficiency or diabe­ their antebrachium, with subse­ soil or dirt of cat fight lacerations tes mellitus may render the cat quent inoculation of virus into the or abrasive injuries to the pads somewhat immunodeficient, while dermis of the nasal bridge. or interdigital spaces. Likewise, the presence of liver or kidney contaminated penetrating wounds dysfunction may affect the selection The main focus of this short note of the caudoventral abdominal of the most appropriate antimicro­ is to alert clinicians to the likely region often result in mycobacterial bial agent(s) or limit doses that can pathogenesis for infections of this panniculitis of the inguinal fat pad. be safely given (e.g., amphotericin B anatomic region. Importantly, even in cats with pre-existing renal insuf­ though saprophytic organisms Diagnostic Evaluation ficiency). A positive FIV-status does generally considered to be of low Investigation of these cases typically not preclude a satisfactory response virulence are isolated from these involves obtaining representative to appropriate therapy, as it is patients, in most cases there is no material for cytology, histology and generally impossible to discern the predisposing immunodeficiency appropriate culture. Cytology and stage and impact of the FIV infec­ state. Thus, the infection merely histology generally show pyogenic tion until after the cat has received reflects a breach in the integrity of or pyogranulomatous inflammation appropriate therapy. Indeed, in the normal cutaneous barriers and an and usually causal organisms can authors’ experience, concurrent FIV especially heavy inoculum of infec­ be visualized using special stains infection is most often an epiphe- tious agent. Unfortunately, these (Diff-Quik, Gram, Ziehl-Neelsen, nomenon in this cohort of patient infections may be difficult to cure, periodic acid Schiff, silver stains). reflecting the cats’ outdoor lifestyle as some causal strains are locally A variety of staining techniques and propensity to fight. invasive and the region does not may be required, and in some cases have an especially rich blood supply an exhaustive search of smears or Therapy or mobile skin nearby to facilitate histologic sections is required to The treatment of these cases involves reconstructive surgical procedures. detect the infectious agents. Myco­ long courses of carefully selected Furthermore, many of these sapro­ bacteria, fungi, and Nocardia species antimicrobials based on accurate phytic organisms dem onstrate resis­ may sometimes be detected in Diff- species identification, in vitro tance to commonly used antimicro­ Quik-stained smears because of a susceptibility data (ideally from bials both in vitro and in vivo, and negative, rather than positive, stain­ a specialist reference laboratory) this can be especially problematic ing reaction. The laboratory should and information from the human for the fungal pathogens. be warned of the possibility of a and veterinary literature avail­ fastidious saprophytic pathogen, as able through electronic databases. One may speculate as to why cat these organisms often have specific Additionally, many of these patients scratch-related infections occur at growth requirements (e.g., special require complete surgical excision this site rather than elsewhere. First­ culture media, reduced tempera­ of grossly infected tissues to assist ly, it is a very commonly involved ture of incubation, requirement for the host’s non-specific immune site. Secondly, it is a location that high carbon dioxide concentration, response. Given the severity of the cats cannot reach with their tongue, etc.) and/or require several days or pathology in long-standing cases whereas scratch wounds elsewhere even weeks to become detectable and the diffusion barriers resulting may be cleansed of potentially as visible colonies in vitro. Ideally, from tissue necrosis and fibroplasia, pathogenic microbes before an a small portion of the biopsy speci­ it is understandable that adequate infection is established. Thirdly, the men should also be frozen in case levels of antimicrobials may not b^ predilection area is sparsely covered polymerase chain reaction tech­ achieved throughout all affecte*. by hair, so injuries from claws may niques or additional culture studies tissues. Thus, the best chance for a penetrate more deeply into the are required at a later date. subcutis compared to areas afforded

-12- successful outcome for certain cats the longest courses of therapy, and Cases with Naso-Ocular Infection is to use an approach reminiscent should ideally be treated not only and Concurrent Signs of Nasal of oncologic surgery, by removing until the lesion appears grossly Cavity Disease s much infected tissue as possible normal, but for an additional period These cases are not the main focus using en bloc resection following exceeding the lifespan of macro­ of this communication, but are preliminary antimicrobial therapy phages in the tissues, i.e., a further included for completeness. In these which is extended into the intra­ two months. Additional informa­ patients, the primary problem starts operative period and continued tion on diagnosis and treatment of with infection of the nasal cavity post-operatively. Residual micro­ representative infections of this type by infectious propagules (typically scopic foci of infection can then be can be found in the bibliography. spores) of saprophytic fungi filtered targeted by the high concentrations by the nasal passages. This may be Prevention of antibiotics achieved during and facilitated by a pre-existing cause Although the vast majority of cat after surgery. of nasal injury. Involvement of the scratch injuries to the face heal naso-ocular region develops subse­ This may be done at the outset without any untoward sequelae, the quent to the infection spreading to (for convenience and to minimize possibility of opportunistic infec­ the nasal planum or penetrating the number of procedures to which tions developing should be borne the overlying bones to reach the the patient must be subjected), or in mind. Thorough cleansing of subcutis over the nasal bridge. after a microbiological diagnosis contaminated scratch wounds using Most of these cases are attributable has been made; e.g., by aspira­ saline or a dilute antiseptic (e.g., 0.05 to cryptococcosis and in many of tion biopsy or resection of a small percent chlorhexidine) would seem these patients the nasal planum is representative tissue specimen. prudent, followed by instillation of affected prominently. We have also In the latter scenario, it is possible an ointment containing both anti­ seen this type of disease progres­ to ensure that effective levels of bacterial and antifungal agents (and sion with invasive aspergillosis appropriate antimicrobial agents without corticosteroids) and possi­ (including Neosartorya spp infec­ are obtained in the peri-operative bly a short course of an antibiotic tions) and rhinitis caused by the Deriod. This may be advantageous such as doxycycline monohydrate termite mycoparasite, Metarhizium ' a major reconstructive procedure (5 mg/kg twice daily for three to anisopliae. Similar findings have is required to remove an extensive five days). Although it is impossible also been reported in a cat with lesion with clear margins. In some to choose an agent with a spectrum invasive bacterial rhinitis caused by cases, surgery alone may be effec­ sufficiently broad to cover all poten- an Actinomyces species. tive in resolving the infection (e.g., tially-pathologic saprophytes, doxy­ Bostock et al., 1982), although cycline has useful activity against These cases can be investigated routine use of follow-up antimi­ many saprophytic mycobacteria, either by directing attention to the crobials is strongly recommended some Nocardia species, oropharyn­ primary site of infection, i.e., the to guard against the possibility of geal organisms such as Pasteurella nasal cavity, by cytological exami­ the surgical margin being seeded spp. and obligate anarobes that may nation of nasal swabs or washings with infectious material. Gener­ have been inoculated simultane­ (e.g., for budding, capsulate yeasts), ally speaking, in the absence of ously via bite wounds. Additionally, serum cryptococcal antigen titer complete surgical excision, these it is generally well tolerated, devoid determinations, anterior/posterior infections require treatment with of significant toxicity (e.g., retino- rhinoscopy, cross-sectional imaging long courses of antimicrobials, at toxicity, nephrotoxicity) and avail­ and biopsy of affected turbinates. least for several weeks, and typically able in conveniently sized tablet Alternatively, needle aspirates or for many months, depending on and paste formulations in Australia, incisional biopsies can be obtained exactly which organism is involved New Zealand and South Africa from the subcutaneous lesions and and how much infected tissue can (VibraVet®; Pfizer Animal Health), submitted for cytologic and histo­ be safely resected at the outset. In which facilitates dosing and owner logic investigations and culture. some cases, combination therapy compliance. The use of a formula­ Invasive mycotic rhinosinusitis with two or more antimicrobials tion containing the monohydrate is generally treated with one or a is superior to monotherapy with a salt is strongly recommended, as combination of antifungal agents ingle agent. Infections caused by it is less irritating to the stomach administered systemically. Although organisms capable of intracellular and esophagus than conventional monotherapy with azoles such survival (e.g., Mycobacteria spp., human formulations utilizing the as itraconazole or fluconazole is Nocardia spp.) and fungi require hydrochloride salt. convenient for owners and effective

-13- in many patients, some cases do not able due to the invasive, granuloma­ our practice, lymphoma is the most respond and require amphotericin tous nature of the infection and the common sinonasal malignancy in B, e.g., as twice weekly subcutaneous propensity in cats for bony erosion the cat, followed by adenocarcinoma infusions, to effect a cure. Unusual (including the cribriform plate) and osteosarcoma, whereas solar fungal infections may sometimes be to occur in association with these induced squamous cell carcinoma more susceptible to other classes of infections. is the most common cancer of the antifungal agent such as terbinafine, nasal planum. The major differential diagnosis or newer azoles such as voricon­ in these cases is invasive nasal azole or posaconazole. Although neoplasia, which can also breach the topical therapy using clotrimazole integrity of overlying nasal bones to “soaks” has been used by others to invade the subcutaneous tissues of treat cases such as this, the authors the nasal bridge and/or forehead. In believe systemic therapy is prefer­

Further Reading 1. Bostock DE, Cohoe PJ, Castellani PJ. (1982) Phaeohyphomycosis caused by E xo p h ia la jea n selm ei in a domestic cat. Journal of Comparative Pathology 92,479-482. 2. Deykin AR, Wigney DI, Smith JS, Young BD. (1996) Corneal granuloma caused by Mycobacterium intracellulare in a cat. Australian Veterinary Practitioner 26, 23-26. 3. Hargis AM, Ginn PE, Mansell JEKL, Garber RL. (1999) Ulcerative facial and nasal dermatitis and stomatitis in cats associated with feline herpesvirus 1. Veterinary Dermatology 10,267-274. 4. Hughes MS, Ball NW, Love DN, Canfield PJ, Wigney DI, Dawson D, Davis PE, Malik R. (1999) Disseminated Mycobacterium genavense infection in a FIV-positive cat. Journal of Feline Medicine & Surgery 1,2 3 -2 9 . 5. Kennis RA, Rosser EJ, Dunstan RW. (1994) Difficult dermatologic diagnosis. [Sporotrichosis in a cat]. Journal of the American Veterinary Medical Association 204, 51 -52 6. Love DN, Malik R, Norris JN. (2000) Bacteriological warfare amongst cats: what have we learned about cat bite infections? V eterinary Microbiology 74, 179-193. 7. McKay JS, Cox CL, Foster AP. (2001) Cutaneous alternariosis in a cat. Journal of Small Animal Practice 42, 75-78. 8. Malik R, Gabor L, Martin P, Mitchell DH, Dawson DJ. (1998) Subcutaneous granuloma caused by Mycobacterium avium complex infection in a cat. Australian Veterinary Journal 7 6 , 604-607. 9. Malik R, Wigney DI, Dawson D, Martin P, Hunt GB, Love DN. (2000) Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings. Journal of Feline Medicine & Surgery 2,35-48. 10. Malik R, Martin P, Davis PE, Love DN. (1996) Localised Corynebacterium pseudotuberculosis infection in a cat. Australian Veterinary Practitioner 26, 27-30. 11. Malik R, Wigney DI, Muir DB. (1994) Phaeohyphomycosis due to E xo ph ia la jea n selm ei in a cat. Australian Veterinary Practitioner 24, 2 7 -3 1. 12. Mark DB. Decision-making in clinical medicine. (2002) In Harrison’s “Principles of Internal Medicine” 15th Edition, Eds Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson, JL. McGraw Hill, New York pp 8-14. 13. Mason KV, Evans AG. (1991) Mosquito bite-caused eosinophilic dermatitis in cats. Journal of the American Veterinary Medical Association 198,2086-2088. 14. Miller DM, Blue JL, Winston SM. (1983) Keratomycosis caused by Cladosporium sp in a cat. Journal of the American Veterinary Medical Association 182, 1121-1122. 15. M uir D, Martin P, Kendall K, Malik R. (1998) Invasive hyphomycotic rhinitis in a cat due to Metarhizium anisopliae. Journal of Medical & Veterinary Mycology 36, 51 -54. 16. Nuttal W, Woodgyer A, Butler S. (1990) Phaeohyphomycosis caused by Exophiala jeanselmei in a domestic cat. New Zealand Veterinary Jo u rn a l 38:123. 17. O’Brien CR, Krockenberger MB, Wigney DI, M artin P, Malik R. (2004) Retrospective study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases. Medical Mycology, 42,449-460 18. Stewart LJ, W hite SD, Kennedy FA, Pavletic MM. (1993) Cutaneous Mycobacterium avium infection in a cat. Veterinary Dermatology 4, 87-90. 19. Yovich JC, Read RA. (1995) Nasal Actinomyces infection in a cat. Australian Veterinary Practitioner 25,114-117.

- 14- Nontuberculous Mycobacterial Syndromes in Cats

Professors Richard Malik,1-2 DVSc, DipVetAn, PhD, FACVSc, FASM, and .'aul J. Canfield,2 DVSC, PhD, FACVSc, Grad Cert Higher Ed FRCPath

'Post Graduate Foundation in Veterinary Science and 2Faculty of Veterinary Science, University of Sydney, Australia

Mycobacterial Panniculitis through some break in the skin. without the characteristic fetid odor This typically follows a penetrating and turbid pus. Instead, a circum­ Rapidly growing mycobacteria injury, especially when the wound is scribed plaque or nodule is apparent. (RGM) are a heterogeneous group contaminated by dirt or soil. Prefer­ Later, there is progressive thickening of organisms that produce colonies ence of RGM for fat is a key factor of the nearby subcutis to which over- on synthetic media within seven in the pathogenesis and results in lying skin becomes adherent. Affect­ days when cultured at 24°C to a tendency for disease to occur in ed areas become denuded of hair and 45°C. They are distributed ubiqui­ obese individuals and in tissues rich numerous punctate fistula appear, tously in nature. RGM include the in lipid, such as the subcutaneous discharging watery exudate. Fistula M. fortuitum group (including AL panniculus and especially the ingui­ are intermingled with focal purple fortuitum, M. peregrinum and the nal fat pad. Experimental infections depressions (thinning of the epider­ 3rd biovariant complex), the AL cannot be induced in cats that do mis over accumulations of pus). chelonae/abscessus group (including not have appreciable subcutaneous The “lesion” gradually increases in M. chelonae and AL abscessus), the fat. Adipose tissue offers a favorable area and depth, and may eventually M. smegmatis group (including AL environment for survival and prolif­ involve the entire ventral abdomen, smegmatis sensu stricto, AL goodii eration of RGM by providing triglyc­ adjacent flanks or limbs. If cats are and M. wolinkskyi) and a variety of erides for growth or by protecting presented promptly for veterinary other species. The taxonomy of this organisms from the phagocytic and attention and the lesion confused group has been revised recently and immune responses of the host. Initial with an anaerobic cat-bite abscess, because of this, the word “group” reports suggested that mycobacterial surgical drainage and administration s used when referring to isolates panniculitis was more common in of a (3-lactam is typically followed by recorded in early publications. RGM warm, humid climates; however, cats wound breakdown and develop­ are strongly linked with localized from temperate regions, including ment of a non-healing suppurat­ infections of immunocompetent parts of Australia, Canada, Finland ing tract surrounded by indurated hosts. This is because they are well and Germany, have subsequently granulation tissue. Some affected adapted to a saprophytic existence been reported. In Australia, the M. cats with infections develop systemic and inherently have low virulence. smegmatis group accounts for the signs, becoming depressed, pyretic, Thus, they do not produce disease majority of feline cases, whereas it is inappetent, losing weight and being unless a breakdown in normal a much less common cause of equiv­ reluctant to move. Occasionally, cats defense barriers provides them with alent infections in human patients. develop the hypercalcemia of granu­ a portal of entry to a favorable tissue lomatous disease, although this is environment. Once introduced, Clinical Signs: Infections tend to rarely symptomatic. Surprisingly, RGM are generally constrained by start in the inguinal region, usually other cats remain comparatively well a vigorous immune response that following contamination of cat- despite extensive disease. Usually the may or may not eradicate them, but fight injuries (e.g., raking wounds problem remains localized to the is effective enough to prevent hema­ inflicted with the hind claws). The skin and subcutis. Although adja­ togenous or lymphatic spread. RGM infection may spread to contiguous cent structures such as the abdomi­ can produce widely disseminated subcutaneous tissues of the ventral nal wall can be affected eventually, disease, but only in severely immu­ and lateral abdominal wall and spread to internal organs or lymph nocompromised individuals. perineum. Penetrating injury by nodes is very unusual. sticks, metallic objects, and vehicu­ Mycobacterial panniculitis refers Diagnosis: Sample collection, lar traum a may also give rise to these to a syndrome characterized by cytology and histology: A tentative infections, as can cat- and dog-bite chronic infection of the subcutis diagnosis of mycobacteriosis can be injuries contaminated with soil or nd skin with RGM. This condi­ confirmed by collection of pus or dirt. Sometimes infections start in tion is quite common in cats, espe­ deep tissue specimens. This mate­ the axilla, flanks, or dorsum. cially in Australia. RGM replicate in rial is used to confirm the diagnosis Early in their course, infections mammalian tissues when introduced using appropriately stained smears, resemble cat-fight abscesses, but -15- histological sections and culture. A to send the strain to a Mycobacte­ histological diagnosis is unnecessary ria Reference Laboratory following if appropriate samples for cytology primary isolation. Identification and culture have been procured. It takes into account a number q is vital to give the laboratory warn­ phenotypic and biochemical features. ing that mycobacterial etiology is Minimum inhibitory concentrations suspected so special procedures for (MICs) for ciprofloxacin, moxi-

processing can be adopted. Extensive lesion in the axilla of a cat floxacin, gentamicin, trimethoprim, In our experience, samples of pus due to a rapidly growing mycobacteria, clarithromycin and doxycycline obtained from needle aspirates of in this instance M smegmatis. can be determined easily using the affected tissues through intact skin pyogranulomatous inflammation Etest (AB Biodisk, Solna, Sweden) provide the best laboratory speci­ and it is generally possible to visual­ method. This methodology is less mens. This material can be obtained ize Gram positive and/or acid-fast demanding than the “gold standard” from a palpably abnormal portion bacilli (AFB) in smears, although an of broth microdilution. Antimicro­ of the subcutis. The overlying skin exhaustive search may be required. bial susceptibility of clinical isolates should be carefully disinfected with Histologically, there is pyogranulo­ can also be determined using disc 70 percent ethanol prior to obtain­ matous inflammation. AFB may be diffusion methodology. ing the specimen to preclude the hard or impossible to find in Ziehl- Therapy: The management of feline isolation of saprophytic mycobac­ Nielsen (ZN) stained tissue sections mycobacterial panniculitis contin­ teria from the skin surface. It may and are often located in lipid vacu­ ues to evolve in the light of clinical be necessary to carefully move the oles. Some United States (U.S.) experience, availability of new anti- needle in the subcutaneous space, dermatologists favor Fites stain for infective agents and the develop­ while applying constant negative detecting AFB in tissues. ment of new surgical techniques. pressure, until a pocket of purulent There is great variation in the sever­ material is encountered. Aspirated Bacteriology and antimicrobial ity and extent of lesions from patient fluid should be submitted for cytol­ susceptibility testing: Tissue to patient. Difficulty in making a ogy and mycobacterial culture, homogenates and pus should be prompt diagnosis is partly respor or inoculated immediately into a streaked onto blood agar plates sible for the chronicity, severity and commercially prepared mycobacte­ and a mycobacterial medium such refractoriness of these infections. ria culture bottle that is subsequently as Lowenstein-Jensen medium Briefly, treatment should commence submitted to the laboratory. It is only or one percent Ogawa egg yolk with oral antimicrobial(s) (doxy­ necessary to suck a small amount of medium and incubated aerobi­ cycline, a flouroquinolone and/or liquid material into the hub of the cally at 37°C and 25°C. If available, clarithromycin), initially chosen syringe. It is easiest to submit the the BACTEC system can also be empirically, but subsequently based entire syringe to the laboratory after utilized. Moderate to heavy growth on in vitro susceptibility data. Some­ replacing the needle with a sterile of pinpoint, non-hemolytic colo­ times long-term administration of cover. Exudate from draining sinus nies is usually detected after two to such an agent or agents is sufficient tracts is heavily contaminated with three days (occasionally longer) on to affect a cure, but in many severe secondary invaders and represents sheep blood agar at 37°C. A useful cases it is eventually necessary to an inferior sample. If deep biopsies method which can be used to surgically resect recalcitrant tissues are obtained, they should be tritu­ differentiate RGM from contami­ so that oral antimicrobial therapy rated in brain heart infusion broth nant flora is by primary isolation will be able to cure the infection using a sterile mortar and pestle to around antibiotic sensitivity discs produce a tissue homogenate suit­ (first generation cephalosporins or able for cytology and culture. isoxazolyl penicillins) applied to the plate after inoculation. Smears prepared from aspirates or tissue homogenates should be There is great value in deter­ stained using Diff-Quik®, Gram mining species identification and stain, and a modified acid-fast susceptibility data in every case, as procedure (decolorizing with ten this has a big impact on antimicro­ percent sulphuric acid for only bial strategies. Species identification can be carried out in a well equipped Even though this is a quoll, the lesions three to five minutes; RGM are not on the ventral abdomen are highly as acid-fast as other mycobacteria). veterinary bacteriology laboratory, suggestive of feline panniculitis due to Cytology invariably demonstrates although it is often more convenient rapidly growing mycobacteria. 16- permanently. Given the extent and mens from mesenteric lymph nodes, severity of the pathology in many liver or kidney at laparotomy, or from of these cases, it is understandable a popliteal lymph node. The primary lat adequate levels of antimicrobi­ antecedent event was most likely als may not be achieved throughout colonization of either the alimentary all affected tissues and that in these or respiratory tract, followed by local cases the best chance for a success­ invasion and eventual lymphatic and ful outcome is to remove as much hematogenous dissemination. infected tissue as possible following Nine cases were treated using preliminary drug therapy. Residual combination therapy with agents Focal lesion on the toe of a cat caused foci of infection can then be targeted effective for MAC infection in by M. lepraem urium . by high concentrations of antibiotics human patients. The results were achieved during and after surgery. M. lepraemurium following bite inju­ generally favorable, although the Peri- and post-operative antimicro­ ries from infected rodents. M. leprae­ disease had a tendency to recur if bial therapy is vital to ensure prima­ murium is a fastidious, slow-grow­ insufficient treatment courses were ry intention healing of the surgical ing organism which, with difficulty, utilized. Cats were generally treated incision. In the future, drugs such can be cultured from large inocula with long courses (five to 14 months) as moxifloxacin and pradofloxacin on Ogawas egg yolk medium under of clarithromycin combined with may prove even more effective than special conditions. Although a few either clofazimine or rifampicin, and agents currently available. investigators have successfully grown a fluoroquinolone or doxycycline M. lepraemurium from infected cats, Disseminated Mycobacte­ was sometimes given also, although the basis of ascribing this bacte­ rium Avium-intracellulare in the future moxifloxacin may prove rium as the etiological agent of feline Complex (MAC) Infection in to be a superior adjunctive agent in leprosy was dependent on transmis­ Young Cats this setting. sion studies. Interestingly, some cats We have recently reported a new Certain lines of Abyssinian and appeared much more susceptible to yndrome of disseminated MAC Somali cats likely suffer from a famil­ experimental infection than others. nfection in ten young cats (one to ial immunodeficiency that predis­ According to the literature, cats five years old) from Australia and poses them to infection with slow- with feline leprosy are typically North America. A further two cats growing mycobacteria such as MAC. young adults (< five years), perhaps with disseminated mycobacteriosis Studies of this problem are ongoing. (precise agent not identified) were with a preponderance of males. recognized also. Of the 12, ten Feline Leprosy Syndromes Presumably, these patient char­ acteristics reflect the need for the were Abyssinian cats, one was a Historical perspective: The term feline cat to interact with a rat to become Somali cat and one was a domestic leprosy is used to refer to a disease infected. The initial lesion is a focal shorthair cat. None of the cats tested in which single or multiple granu­ granuloma of the subcutis. Owners positive for either FeLV antigen or lomas form in the skin or subcutis become aware of solitary, or more FIV antibody. in association with large numbers commonly, multiple, painless, raised, The clinical course of these infec­ of acid-fast bacilli (AFB) which are fleshy, tumor-like lesions, from a few tions was indolent, with cats typi­ nonculturable using standard meth­ millimeters up to four cm in diam­ cally presenting for weight loss, ods. The condition was first recorded eter. These granulomas are freely initially in the face of polyphagia, in the literature by Australian and movable over underlying tissues. with a chronicity of up to several New Zealand researchers in the early Lesions can develop rapidly and months. Additional clinical features 1960s. Since then, the disease has when large, may ulcerate. Infection included lower respiratory tract been reported in Western Canada, spreads to adjacent areas and may signs and peripheral lymphadeno- the Netherlands, France, the United invade underlying tissues and drain megaly. A marked diffuse intersti­ Kingdom and the U.S. tial pattern was evident in thoracic to regional lymph nodes. Lesions radiographs, even in cats without Historically, the causative agent of can occur anywhere, but tend to be overt respiratory involvement. Hair feline leprosy was purported to be concentrated on the head and limbs. Upped to perform diagnostic proce­ Mycobacterium lepraemurium. This Small lesions are occasionally found dures tended to regrow slowly, if at bacterium causes murine leprosy, a on the tongue, lips, and nasal plane. all. Diagnosis was generally made by systemic tuberculosis-like infection Lesions, even if multiple, tend to be obtaining representative tissue speci­ of rats. Cats are thought to contract initially concentrated in one region

-17- and have the propensity to recur The second group consisted of following excision. Enormous old cats (>nine years) with general­ numbers of ized nodular skin lesions associated Pathologically, feline leprosy acid fast bacilli are with multibacillary lepromatoc was subdivided into lepromatous evident in an histology. Some cats initially had or tuberculoid forms based on the aspirate from localized disease that subsequently a nodule of a number of AFB present (multi- became widespread, while others cat with the bacillary vs. paucibacillary) and novel NSW had generalized disease from the the host immunological response species. outset. Disease progression was (lepromatous vs. tuberculoid). protracted, typically taking months Because the causal mycobacteria to years, and skin nodules did not are slow-growing organisms capable ulcerate. Microscopically, lesions of intracellular survival, the histo­ consisted of sheets of epithelioid Of the remaining cases, one cat had logic picture actually depends on macrophages containing large to a disseminated M. avium infection, the host’s immune response. When enormous numbers of AFB 2-8 pm the etiology in one cat was unde­ this response is poor, lepromatous (mostly 4-6 pm), which stained termined and in two cases infection (multibacillary) disease develops also with hematoxylin. A single was attributable to a novel myco­ with infiltration of the dermis with unique sequence spanning a 557 bacterial species. This information large sheets of “incompetent” foamy bp fragment of the 16S rRNA gene encouraged a reappraisal of Austra­ macrophages containing enormous was identified in lesions from these lian feline leprosy cases, and subse­ numbers of organisms. AFB are patients. The sequence was charac­ quently this work has been extended usually arranged in the cytoplasm of terized by a long helix 18 in the V3 to North America by groups lead by macrophages as dense parallel accu­ region, suggesting the new species Greg Appleyard and Janet Foley. mulations which displace the nucleus was likely to be a fastidious, slow- to an eccentric position. Lymphoid In Australia, cats were initially grower. The 16S rRNA sequence had cells and plasma cells are virtually divided into two groups based on the greatest nucleotide identity with absent from the lesions. If the hosts the patients’ age, lesion histology, M. leprae, M. haemophilum, and M im m une response is more effective, clinical course and sequence of 16S malmoense, and contained an add. histiocytic cells are accompanied by rRNA PCR amplicons obtained tional “A” nucleotide at position 105 moderate num bers of lymphoid cells from lesions. More recently, we have (the only other mycobacterial data­ and plasma cells and multiplication identified a new cohort of Australian base sequence with the same extra of the organism is limited—the so- cats from the Gippsland region of nucleotide being M. leprae). A very called tuberculoid response. Victoria which were infected by a slow, pure growth of a mycobacteri­ third novel mycobacterial species. um species was observed on Lowen- AFB in smears and tissue sections stein-Jensen medium (supplemented appear as long slender rods. In The first group consisted of young with iron) and semisolid agar in one smears stained with Romanowsky cats (typically

-18- of rural Victoria. The distribution immune deficient cats. Sequence which may limit the success of the of lesions is most compatible with a analyses demonstrate a number of procedure. Recently, Hughes and saprophytic organism being inocu- nucleotide differences between M. colleagues have developed specific ted in tissues subsequent to cat visibilis and both M. lepraemurium PCR assays to diagnose infections scratch injuries. and the novel species reported by due to M. lepraemurium and the Hughes et al. novel species; furthermore, use of The presence of tuberculoid a simple restriction enzyme digest pathology is generally a marker of Diagnosis: Diagnosis of the “feline allows these assays to distinguish M. disease in an immune-competent leprosy” syndromes is usually visibilis strains also. host, and such infections are often straightforward, provided that the initially localized. In contradistinc­ clinician has a high index of suspi­ Therapy: Too few cases with a docu­ tion, the presence of a foamy histio­ cion for the condition. Needle aspi­ mented etiology have been reported cytic infiltrate of the dermis and rates, crush preparations of biopsy to provide definitive treatment subcutis in patients with mycobacte­ material and histological sections guidelines. Although M. lepraem­ riosis is observed almost exclusively stained with ZN or similar methods urium and the novel species can be in association with profound immu­ contain easily demonstrable AFB cultured in vitro with difficulty, it is nodeficiency, such as that seen with surrounded by variable granuloma­ currently not routine or reliable to terminal HIV infection in human tous to pyogranulomatous inflam­ isolate these organisms due to their patients. Widespread dissemina­ mation. In Diff-Quik stained smears, slow growth and fastidious require­ tion of infection (rather than local mycobacteria can be recognized by ments. Determination of in vitro invasion) suggests decreased immu­ their characteristic “negative-stain­ susceptibility data for individual nological surveillance permits the ing” appearance and location within isolates is therefore not possible. development of disease with an macrophages and giant cells. Only limited experimental stud­ organism usually considered to have Material should be submitted ies have been undertaken to deter­ limited virulence. Feline leprosy also for culture because occasion­ mine effective drug therapy for M. caused by the novel NSW mycobac­ ally slowly-growing species such lepraemurium in vitro or in vivo and terial species, the Victorian novel as MAC, M. genavense and the as yet we have limited data only for lecies or more rarely M. leprae­ tubercle bacillus (M. bovis or M. the novel mycobacterial species. murium, may likewise represent microti) can produce an identical Portaels and colleagues found the a manifestation of deteriorating clinical presentation. In such cases, minimum inhibitory concentration immune competence. optimal antimycobacterial therapy for rifampicin of two strains of M. can be selected more readily on the lepraemurium to be 4 and 8 pg/ml, For epidemiologic reasons, feline basis of in vitro susceptibility results levels that should be just obtainable leprosy in young cats is almost and information available in the in vivo. Other drugs shown to have invariably caused by M. lepraem­ literature. In the majority of cases, activity against M. lepraemurium in urium, the novel NSW species is however, conventional mycobacte­ vitro include ansamycin compounds almost invariably seen in old (likely rial culture is negative due to the (rifabutin) and sulpha drugs. There immunosuppressed cats) while the fastidious nature of the causal organ­ is a good deal of clinical evidence novel Victorian species can occur isms, and the exact etiology can only that clofazimine has efficacy in vivo, in either immune-competent or be proven using PCR amplification while it is likely that clarithromycin immune-defective cats. and sequence determination of gene would also be effective based on its wide spectrum of activity against To make matters even more fragments. PCR has the additional slow-growing mycobacterial species. complex, work by Appleyard and advantage of providing a rapid diag­ Clark (2002) demonstrated a third nosis. Fresh (frozen) tissue delivered to a mycobacterium laboratory with The literature suggests that mycobacterial syndrome in cats when M. lepraemurium infection from western Canada and the U.S. PCR facilities provides the optimal sample, although freeze-dried speci­ is diagnosed early, while disease is (Idaho and Oregon) called “feline localized, wide surgical excision of mens may be more conveniently multisystemic granulomatous myco­ infected tissues provides the best sent where tissues need to travel long bacteriosis.” This disease is caused chance to simply and rapidly affect distances. Sometimes PCR can be by a slow-growing taxa provision- a cure. Aggressive resection tech­ ly called M. visibilis or M. visible. performed successfully on formalin- fixed paraffin-embedded material, niques should be adopted, with en this species is capable of producing bloc resection of all lesions, and although fixation conditions invari­ widespread dissemination to multi­ reconstruction of resulting tissue ably cause some DNA degradation ple internal organs, presumably in deficits using appropriate surgi­ -19- cal techniques. Such an approach drugs, doxycycline, new fluoroqui­ represents optimal therapy. Howev­ should be combined with adjunct nolones such as moxifloxacin or er, we are currently unsure of which antimicrobial therapy beginning a pradofloxacin, or amikacin may in will prove to be the best combina­ few days prior to surgery, so that time also prove to be useful. Unfor­ tion, and side effects in individu effective levels of drugs are present tunately, clofazimine is becoming cats may affect which two drugs are in blood and tissues intra- and post- very difficult to obtain, although used in a given patient. Currently, we operatively to ensure primary inten­ some compounding pharmacies can recommend a combination of rifam­ tion healing. Clofazimine (at a dose source the dye. picin and clarithromycin as initial of up to 10 mg/kg once daily orally; therapy. The new quinolone moxi­ In feline leprosy cases caused by typically 25 to 50 mg every 24 to 48 floxacin may prove useful in future novel mycobacterium species, we hours) has the best reported success cases, as it has good antimycobacte- believe combination therapy using rate, although it is likely that combi­ rial activity and is affordable. Other two or three drugs including clofazi­ nation therapy using two or more new agents such as linezolid may mine (25 to 50 mg per cat orally drugs will eventually prove superior. also have a place, although currently every day or every other day), clar­ Drugs that could be combined with they are prohibitively expensive for ithromycin (62.5 mg twice daily) or clofazimine include rifampicin and most owners. rifampicin (10 to 15 mg/kg per day) clarithromycin, although sulpha

Further Reading 1. Appleyard, G.D., & Clark, E.G. (2002) Histologic and genotypic characterization of a novel Mycobacterium species found in three cats. Jo urn a l of Clinical Microbiology 40:2425-2430. 2. Baral, R.M., Catt, M J., Foster, S.F., McWhirter, C., Wigney, D.I., M artin, P., Chen, S.C.A., Mitchell, D.H. and Malik R. (2006) Disseminated Mycobacterium avium infection in young cats: over-representation of Abyssinians. Journal of Feline Medicine & Surgery 8:23-44. 3. Davies, J.L., Sibley, J.A., Myers, S., Clark, E.G., Appleyard, G.D. (2006) Histological and genotypical characterization of feline cutaneous mycobacteriosis: a retrospective study of formalin-fixed paraffin-embedded tissues. Veterinary Dermatology 17:155-162. 4. Foster, S.F., M artin, P., Davis, W., Allan, G.S., Mitchell, D.H. 8t Malik R. (1999) Chronic pneumonia caused by Mycobacterium thermoresistible in a cat. Journal of Small Animal Practice 40:433-438. 5. Hughes, M.S., Ball, N.W., Love, D.N., Canfield, P.J. Wigney, D.I., Dawson, D„ Davis P.E. 8; Malik, R. (1999) Disseminated Mycobacterium genavense infection in an FIV-positive cat. Journal of Feline Medicine & Surgery 1:23-30. 6. Hughes, M.S., James, G„ Taylor, M.J., McCarroll, J., Neill, S.D., Chen, S.C.A., Mitchell, D.H., Love, D.N., Malik, R. (2004) PCR studies of feline leprosy cases. Journal of Feline Medicine & Surgery 6: 235-243. 7. Hunt G.B., Tisdall P. L. C„ Liptak J. M„ Beck J.A., Swinney G.R., Malik R. (2001) Skin-fold advancement flaps for closing large proximal limb and trunk defects in dogs and cats. Veterinary Surgery 30:440-448. 8. Malik R„ Wigney, D.I., Dawson, D„ Martin, P., Hunt, G.B., 8t Love, D.N. (2000) Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings. Journal of Feline Medicine & Surgery 2:35-48. 9. Malik, R„ Hughes M.S., James, G., Chen, S.C.A., Mitchell, D.H., Wigney, D.I., Matrin, P., Canfield, P.J. & Love, D.N. (2002) Feline leprosy: two different clinical syndromes. Journal of Feline Medicine & Surgery 4:43-59. 10. Fyfe, J.A., McCowan, C., OBrien, C.R., Globan, M„ Birch, C., Revill, P., Barrs, V.R.D., Wayne, J., Hughes, M.S., Holloway, S., Malik, R. (2008) Molecular characterization of a novel fastidious mycobacterium causing lepromatous lesions of the skin, cornea, and conjunctiva of cats living in Victoria, Australia. Journal of Clinical Microbiology 46:618-626.

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