CASE REPORTS

Clinical Resolution of Nasal Aspergillosis Following Therapy with a Homeopathic Remedy in a Dog
Shelley Epstein, VMD, Robert Hardy, DVM, MS, DACVIM

ABSTRACT
A 6 yr old, male, neutered Weimaraner was treated homeopathically for nasal aspergillosis after failing to respond to two treatments of topical (intranasal) clotrimazole and oral amoxicillin trihydrate/clavulanate potassium. Computed tomography, rhinoscopy, fungal culture, and cytology previously conrmed the diagnosis. At presentation for homeopathic treatment, the dog had aggressive left-sided sinusitis and rhinitis with destruction of nasal turbinates and severe bouts of epistaxis. Erosion and depigmentation of the nasal planum were evident. After two treatments with homeopathic aurum metallicum, resolution of clinical signs occurred and clearance of the aspergillosis organisms was documented by computed tomographic scan, rhinoscopy, and histopathology. Homeopathic aurum metallicum may be benecial in treating cases of canine nasal aspergillosis.
(J Am Anim Hosp Assoc 2011; 47:e110e115. DOI 10.5326/JAAHA-MS-5560)

Introduction
Aspergillosis is a common cause of nasal infection in the dog, affecting between 12% and 34% of dogs evaluated for chronic sinonasal disease.1 It can cause a profuse mucopurulent to hemorrhagic nasal discharge, sneezing, reverse sneezing, ulceration of the external nostrils, facial pain or discomfort, destruction and necrosis of the nasal mucosa and underlying turbinate bones, and frontal sinus osteomyelitis.
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one treatment and an 8687% success rate with one or more applications.9,10 More recently, endoscope-assisted debridement followed by endoscope-assisted infusions with 1% or 2% enilconazole were evaluated. The overall success rate of treatment of dogs in either group (9 of 19 [47%] cured after one infusion, 6 of 19 [32%] after two infusions, and 2 of 19 [11%] after three infusions of 1% enilconazole [total 89%]; 6 of 7 [85.7%] cured after one infusion; the remaining dog cured after a second infusion of 2% enilconazole) was similar to that previously reported for noninvasive topical infusions.3 Another recent study evaluated the efcacy of a 5 min ush of 1% clotrimazole delivered via frontal sinus trephination followed by instillation of a 1% clotrimazole cream. Twelve of the 14 dogs (86%) responded well to treatment and either had no clinical signs after treatment or had signs consistent with mild rhinitis during a minimum follow up of 6 mo. Only one dog required multiple treatments.11 This treatment protocol, although offering comparable success rates and shorter anesthesia than intranasal infusions of either clotrimazole or enilconazole delivered via catheters, is more invasive and carries additional expense. For dogs that remain refractory to
CT computed tomography

Effective, noninvasive, safe, and

inexpensive treatment of dogs diagnosed with nasal aspergillosis is challenging. Oral administration of antifungal agents such as thiabendazole, ketoconazole, itraconazole, and uconazole, although noninvasive, requires prolonged administration due to poor to moderate efcacy.48 In addition to the high cost of these drugs, side effects such as hepatotoxicosis, anorexia, and vomiting are commonly reported.7 Clinical cure is reported in approximately half of the patients treated with thiabendazole and ketoconazole, and in as many as 70% of patients treated with itraconazole or uconazole.
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A topical 1 hr infusion with clotrimazole is considered an effective noninvasive treatment that carries a 65% success rate after
From the Wilmington Animal Hospital, Wilmington, DE (S.E.); and College of Veterinary Medicine, University of Minnesota, St. Paul, MN (R.H.). Correspondence: 4epsteins@comcast.net (S.E.)

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any treatment, rhinostomy and topical povidine-iodine dressings or rhinotomy combined with surgical debridement and topical administration of 2% enilconazole may be indicated.
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of the nasal planum, lack of airow through the left nostril, and blood-tinged serous nasal discharge on the left side that changed to a mucopurulent discharge after a bout of sneezing. The left submandibular lymph node was enlarged. Temperature, pulse, and respiration were normal (38.88C, 120 beats/min, and 20 breaths/ min, respectively), as was a neurologic examination. A complete blood count and serum biochemical prole were submitted. The only signicant laboratory abnormalities were hypoproteinemia (5.2 g/dL; reference range 5.77.5 g/dL) and hypoalbuminemia (2.3 g/dL; reference range 2.73.7 g/dL). On day 2, nasal computed tomography (CT) and rhinoscopy were performed. Extensive turbinate destruction was identied by CT a within the rostral and midnasal passages on the left side. Multifocal, patchy areas of uid and thickened soft tissue material were present, predominantly on the left side, but with some similar appearing material on the right side. There was no evidence of frontal sinus or maxillary bone destruction. Mild bone thickening of the lateral ventral aspect of the left frontal sinus was present. The cribriform plate was intact. Mild left-sided retropharyngeal and submandibular lymphadenopathy were present. No other abnormalities were seen. The diagnostic interpretation was chronic destructive left-sided rhinitis and sinusitis with mild right-sided rhinitis and secondary lymphadenopathy. A fungal disease was suspected; differentials included aspergillosis and other fungal agents (Figure 1).

Homeopathy is a system of medicine developed by the German physician Samuel Hahnemann (17551843). It is based on the principle of let like cure like. Substances, when tested, can cause a set of symptoms in healthy individuals that are used to cure those symptoms (signs in animals) when experienced by sick individuals. The tests are known as provings and are conducted using dilutions of the original substance.14 One of the rst substances tested by Hahnemann was a preparation of gold, aurum metallicum, in 1818 (six grains triturated in 100 grains of milk sugar for 1 hr, then 100 grains of this powder [1 grain of gold] or 200 grains of this powder [2 grains of gold] dissolved in water [amount not specied] and given orally to the human provers). This testing, along with his subsequent prescribing of aurum metallicum to sick individuals (one part of gold triturated to 100 parts of milk sugar, then one part of this to 100 additional parts of milk sugar, nal dilution 1/10,000, given orally, amount not specied), led him to discover the curative use of aurum metallicum for painful, ulcerated nasal cavities and nostrils, nasal congestion, greenish yellow nasal discharge, and destruction of the palatal and nasal bones.
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The purpose of this report is to describe a case of nasal aspergillosis in a dog in which oral administration of homeopathic aurum metallicum resulted in resolution of signs and disappearance of the aspergillosis organisms after two noninvasive clotrimazole infusions had been unsuccessful. This is the rst reported case of clinical resolution of nasal aspergillosis after treatment with aurum metallicum in which follow-up studies were performed to document the physical changes and clearance of the aspergillosis organisms.

Case Report
A 6 yr old, 33 kg, male, neutered Weimaraner was presented to the University of Minnesota Veterinary Medical Center (VMC) for evaluation of a 68 mo history of left-sided nasal discharge, sneezing, and a 3 yr history of episodes of reverse sneezing. The nasal discharge initially was clear to mucoid, but became purulent with occasional mild epistaxis approximately 3 mo before presentation. The clinical signs were unresponsive to treatment with oral diphenhydramine and clindamycin. During the 4 mo period before presentation to the University of Minnesota VMC, the dog became progressively more lethargic, and 12 mo before presentation, he developed a snapping at ies behavior accompanied by continuous licking and crusting of the dorsal nasal planum. Physical examination on day 1 showed a small amount of crusting on the dorsal nasal planum, erosion and depigmentation
FIGURE 1

Nasal computed tomographic (CT) scan on day 2,

before clotrimazole infusion. Increase in soft tissue and uid density material as well as loss of normal turbinate architecture are present.

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Rhinoscopy, using both a 2.7 mm Stortz rigid telescopeb for proximal visualization and an Olympus Exera II exible videoendoscopec for the retroexed views of the nasopharynx, showed a thick ropey discharge in the left nasal passage, loss of nasal turbinates, hyperemia, and edema. Fungal plaques were visible in the left nasal passages and nasopharyngeal meatus (Figure 2). The right nasal passage was erythematous and edematous with no turbinate destruction. Nasal biopsies were obtained with a 2.5 mm exible cup forcep biopsy instrument passed adjacent to the rigid
d

On day 38 after the initial examination, the owner reported recurrence of sneezing and left-sided nasal discharge, which had ceased entirely for 3 wk immediately after the clotrimazole infusion. Amoxicillin trihydrate/clavulanate potassium was again prescribed for 14 days; however, the discharge continued and worsened. On day 50 after the initial examination, the dog experienced a severe episode of epistaxis. On day 71 after the initial examination, the dog presented again to the University of Minnesota VMC with persistent sneezing, nasal discharge, epistaxis, and facial pain. On the physical examination performed on day 71 after initial presentation, the dog was afebrile (38.88C) and had a left-sided serous nasal discharge, depigmentation of his nasal planum, and crusting on the dorsal nasal planum. The owner declined a second rhinoscopy before a second 1% clotrimazole infusion was administered due to nancial constraints. Clotrimazole was again infused into each nasal passage as previously performed on day 2. The dog was discharged with amoxicillin trihydrate/clavulanate potassium (11.4 mg/kg PO q 12 hr for 14 days). One week later, the owner reported a left-sided thick, yellow, ropey discharge and another episode of epistaxis. The dog also appeared to be experiencing facial pain. The dog was re-evaluated on day 115 (44 days after the second treatment) by SE. A profuse yellowbrown odorous left-sided nasal discharge was present, which persisted throughout the time after the second clotrimazole infusion. In addition, the ulceration and crusting of his nasal planum had progressed (Figure 3). The dog continued to receive amoxicillin trihydrate/clavulanate potassium since day 98. The primary care veterinarian gave two rells for 2 wk

telescope. Cytology of the nasal discharge showed a moderate to marked mixed inammation (neutrophils, small lymphocytes, plasma cells) and the presence of fungal organisms 58 mm in diameter; these were basophilic and forming septate hyphae. Histopathology showed severe brinosuppurative rhinitis with marked inltrates of neutrophils and debris, large areas of necrosis, and extensive amounts of fungal organisms characterized by branching hyphae. A fungal culture yielded growth of Aspergillus spp. A 1 hr, 1% clotrimazolee infusion was performed according to standard technique immediately after the CT scan and rhinoscopy.9 Before the clotrimazole infusion, both nasal passages were ushed antegrade and retrograde with saline . Aggressive def

bridement of visible fungal plaques was not performed, as this was not known to be essential for treatment success at the time of this rhinoscopy.4 The dog was discharged later the same day. Five days later, due to the persistence of the nasal discharge and concern for secondary bacterial infection, amoxicillin trihydrate/clavulanate potassium was prescribed (11.4 mg/kg PO q 12 hr for 14 days).
g

FIGURE 2

Nasopharynx on day 2. Retroexed view with white

FIGURE 3

plaques obstructing the left choanal area. Day 119. Severe ulceration, erythema, and crusting of

the nose of the dog before the aurum metallicum administration and after two clotrimazole infusions.

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each (total of 6 wk). The dog exhibited pain when chewing and was acting cold on his walks, wanting to turn around to go home. On day 119, the homeopathic remedy aurum metallicum 30c was prescribed (5 pellets [size #38] dissolved in 15 mL of water PO once, and then again one time 12 hr later). Improvement was noted by the owner in the rst week. Over the next 3 wk, the epistaxis episodes ceased entirely, the nasal discharge gradually resolved, and the dogs disposition, appetite, and energy returned to normal. Seven weeks after the homeopathic remedy administration, the dog presented for a follow-up CT scan and rhinoscopy at the University of Minnesota VMC. White blood cell count, hematocrit, platelet estimate, red blood cell and white blood cell morphology, total plasma protein, and serum biochemical prole were within normal limits. The previously reported hypoalbuminemia and hypoproteinemia had resolved (albumin, 2.7 g/dL and total protein, 6.6 g/dL). The CT scan showed that the previously noted turbinate thickening on the left nasal passage was no longer present. A few atrophied turbinates were present in the rostral nasal passages, but the majority of the turbinates in the left nasal passage were completely absent (Figure 4). In the caudal nasal passages, the ventral ethmoid turbinates remained, whereas the dorsal turbinates were absent. The surrounding bone was thickened, and edematous soft tissue was present at the periphery. The retropharyngeal lymph nodes appeared normal in size, and the left submandibular lymph
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node was only mildly enlarged with respect to the right. These ndings indicated that progressive destruction of the left nasal turbinates occurred between the rst and second CT scans. The adjacent bone and soft tissue thickening suggested the presence of residual disease. Rhinoscopy, with a 2.7 mm rigid telescope, veried the lack of normal turbinate architecture. Minimal hyperemia or discharge was visible within the left or right nasal passages, and no fungal plaques were visualized. Mucosal biopsies were taken from multiple sites in the left and right nasal passages. Histopathology did not reveal fungal organisms, and mild residual lymphoplasmacytic rhinitis was present. Three to 4 mo later, the owners observed a crusty rough appearance to the dorsal aspect of the dogs nasal planum, and a greenish, brownish, yellowish nasal discharge in the morning that progressed from an occasional drip to a more persistent clear drainage during the day. They also observed a slight recurrence of reverse sneezing and the biting at ies behavior, both of which had resolved after the homeopathic treatment. The owners were instructed to repeat the aurum metallicum as previously prescribed. Within a week of beginning administration of the aurum metallicum, all of the dogs abnormal clinical signs resolved, according to the owner. At follow up on day 965 after initial presentation, the dog remained asymptomatic, with only an occasional reverse sneeze (Figure 5).

FIGURE 5 Dogs nose 7 mo after the initial aurum metallicum

therapy. Some permanent remodeling of the left nasal planum is

FIGURE 4

Nasal CT scan on day 164, 45 days postaurum

present.

metallicum. Signicant loss of nasal turbinates is evident as well as mild thickening of residual nasal mucosa.

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Discussion
Nasal aspergillosis is a common cause of nasal infection in the dog, accounting for up to 34% of dogs with chronic nasal disease.1,16,17 Young to middle-aged dolichocephalic and mesaticephalic dogs are most commonly affected, similar to the dog described in this report.1 The fungal agent most commonly associated with the disease is Aspergillus fumigatus, although A niger, A avus, A nidulans, and Penicillium sp. are occasionally involved. Diagnosis of nasal aspergillosis is based on various combinations of diagnostic tests, including diagnostic imaging, rhinoscopy, sinuscopy, histologic examination, cytology, fungal culture, and serology.18 In the dog described in this case report, a fungal plaque was visualized via rhinoscopy and cultured positive for Aspergillus spp. Fungal elements compatible with Aspergillus spp. were also seen on cytology and further conrmed from biopsies obtained via rhinoscopy. CT imaging also revealed changes compatible with nasal aspergillosis.1921 Initial treatment consisted of two infusions of topical clotrimazole without aggressive debridement. At the time this procedure was performed in this dog, debridement was not part of the standard protocol at the University of Minnesota VMC. It is possible that one reason for this dogs treatment failure was the lack of removal of as many fungal plaques as possible during the rhinoscopy, which was performed only at the time of the rst infusion. A favorable response to conventional therapy is usually indicated by resolution of nasal discharge by 2 wk after therapy.9 Rapid resolution of nasal pain, sanguinous discharge or epistaxis, and ulcerated nares should occur. In some dogs, a mild mucopurulent, crusty discharge may persist at one or both nostrils, presumably as a result of the damaged nasal architecture.1 The dog in this report had a short-lived response after the rst clotrimazole infusion, but by 5 wk postinfusion, clinical signs recurred. The dog showed no response to the second infusion. Repeat treatment is indicated if the nasal discharge persists by 2 wk after therapy.1,9 An additional clotrimazole infusion was not performed as the owners elected to pursue homeopathic treatment. Homeopathic remedies are prescribed based on the concept of let like cure like. A substance is given to healthy human provers, who then record their mental, emotional, and physical symptoms that arise as a result of the remedys effects. The symptoms are collated and recorded in materia medicas and repertories. Symptoms and diseases that have been cured by remedies are also recorded in these texts. These symptoms are then used as indications for the remedy to be administered when a sick patient presents with these symptoms (or signs in the case of an animal).
1

In selecting the appropriate remedy, emphasis is given to signs that are strong in the case (bone destruction, erosion of the nasal planum, yellow malodorous nasal discharge) as well as signs that differentiate one patient from another. Of special importance are modalities, which include anything that makes a patient better or worse, such as hot/cold weather, hot/cold compresses, time of day, and seasons of the year. In this case, the dogs symptoms resolved after administration of aurum metallicum, a homeopathic preparation derived from gold. The dogs signs of bone necrosis, including head pain, ulcerated nostrils, yellow and malodorous nasal discharge, and aggravation from being cold, corresponded with the signs documented for aurum metallicum indications in the homeopathic provings and materia medicas.15,22,23 In this case report, the dog was given a preparation diluted 1:100, 30 times. Homeopathic treatment is not fully dependent upon delineation of an etiological agent. The characteristic symptoms produced by the patient, regardless of the etiological agent, are used for determining the remedy. However, insofar as certain etiologic agents are known to produce xed clinical signs in patients, knowing that Aspergillus spp. were present in this dog could be useful in determining the curative remedy. The results of the CT scans and rhinoscopy, in describing the extent of the pathology in this dog, were helpful in selecting the curative remedy. After oral administration of the homeopathic remedy aurum metallicum, the dog in this report experienced a dramatic clinical improvement and disappearance of the Aspergillosis organisms. Homeopathic treatment of nasal aspergillosis has been reported once previously.
24

The dog in that report had a well-documented

case of nasal aspergillosis and showed an immediate curative response to homeopathic therapy using the same remedy as in this case. Although clinical signs appeared to resolve permanently in that dog, the report did not include any follow-up studies.24 In the case described here, follow-up studies, performed 7 wk after the homeopathic remedy was given and all clinical signs of nasal discharge resolved, showed that turbinate destruction on the left side had progressed between the rst CT, rhinoscopy, and clotrimazole infusion and the second CT and rhinoscopy. Although the CT evidence supported that the disease continued to progress sometime between the rst and second CT examinations, because the patient had persistent signs consistent with nasal aspergillosis after a second clotrimazole infusion and only showed resolution of disease activity after the homeopathic remedy, the authors believed most of the anatomic changes visualized on the second CT reected damage that occurred before the homeopathic remedy. The negative fungal culture and histopathology obtained after the homeopathic remedy supported that the disease was in complete remission at that time.

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The dog in this case had a mild relapse of signs 5 mo after the homeopathic treatment. Given the brief and much milder presentation at that time, no diagnostics were done to verify whether this was a recurrence of nasal aspergillosis. After the second treatment with aurum metallicum, the signs promptly and permanently resolved. The selection of a homeopathic medicine for a specic patient is based on the patients unique characteristic manifestation of the illness versus the etiological agent. However, as the clinical presentation of nasal aspergillosis in the dog remains relatively constant, a narrow selection of homeopathic remedies might be useful. Further pilot studies of the effects of aurum metallicum on nasal aspergillosis, similar to a recently conducted study that used individualized homeopathy to treat pruritus associated with atopic dermatitis in dogs, are indicated.25 The results of such a study would help determine the most useful homeopathic remedies for treatment of nasal aspergillosis. Further studies, ideally using doubleblinded, placebo-controlled clinical trials, could then be conducted. This case report was observational in nature but, in light of the previously reported case, suggested that further study of the use of aurum metallicum in cases of canine nasal aspergillosis should be conducted. This case report was supported in part by a grant from the American Holistic Veterinary Medical Association.
FOOTNOTES a GE HiSpeed CT/e spiral single-slice scanner; GE Healthcare, Waukesha, WI b 2.7 mm Storz rigid telescope; Karl Storz Veterinary Endoscopy, Goleta, CA c Olympus Exera II exible videoendoscope; Olympus America Inc., Center Valley, PA d Flexible cup forcep biopsy instrument; Olympus America Inc., Center Valley, PA e Lotrimin; Schering Corporation, Kenilworth, NJ f Saline; Baxter Corporation, Deereld, IL g Clavamox; Pzer Animal Health, Exton, PA h Boiron, Newtown Square, PA REFERENCES 1. Sharp NJ. Canine nasal aspergillosis-penicilliosis. In: Greene CE, ed. Infectious diseases of the dog and cat. 2nd ed. Philadelphia: WB Saunders Co; 1998:4049. 2. Davidson AP, Pappagianis D. Treatment of nasal aspergillosis with topical clotrimazole. In: Bonagura JD, ed. Kirks current veterinary therapy XII small animal practice. Philadelphia: WB Saunders Co; 1995:899901. 3. Zonderland JL, Stork CK, Saunders JH, et al. Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs. J Am Vet Med Assoc. 2002;221:14215.

4. Peeters D, Clercx C. Update on canine sinonasal aspergillosis. Vet Clin North Am Small Anim Pract. 2007;37(5):90116, vi. 5. Harvey CE. Nasal aspergillosis and penicilliosis in dogs: results of treatment with thiabendazole. J Am Vet Med Assoc. 1984;184(1): 4850. 6. Sharp NJ, Sullivan M. Use of ketoconazole in the treatment of canine nasal aspergillosis. J Am Vet Med Assoc. 1989;194(6):7826. 7. Legendre A. Antimycotic drug therapy. In: Bonagura J, ed. Kirks current veterinary therapy XII small animal practice. Philadelphia: WB Saunders Co; 1995:32731. 8. Sharp NJH, Harvey CE, Obrien JA. Treatment of canine nasal aspergillosis/penicilliosis with uconazole. J Small Anim Pract. 1991; 32:5136. 9. Davidson AP, Mathews KG. CVT update: therapy for nasal aspergillosis. In: Bonagura JD, ed. Kirks current veterinary therapy XIII small animal practice. Philadelphia: WB Saunders Co; 2000: 3157. 10. Smith SA, Andrews G, Biller DS. Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole. J Am Anim Hosp Assoc. 1998;34(6):48792. 11. Sissener TR, Bacon NJ, Friend E, et al. Combined clotrimazole irrigation and depot therapy for canine nasal aspergillosis. J Small Anim Pract. 2006;47(6):3125. 12. Pavletic MM, Clark GN. Open nasal cavity and frontal sinus treatment of chronic canine aspergillosis. Vet Surg. 1991;20(1):438. 13. Claeys S, Lefebvre JB, Schuller S, et al. Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole. J Small Anim Pract. 2006;47(6): 3204. 14. Hahnemann S. Acquiring a knowledge of medicines. In: OReilly WB, ed. Organon of the medical art. Redmond, Washington: Birdcage Books, 1996;723, 15261. 15. Hahnemann S. Aurum metallicum. In: Materia medica pura. New Delhi: B. Jain Publishers (P) Ltd; 2007;17997. 16. Sharp NJH, Harvey CE, Sullivan M. Canine nasal aspergillosis and penicilliosis. Compend Contin Educ Pract Vet. 1991;13:419. 17. Saunders JH, van Bree H. Diagnosis of nasal aspergillosis in the dog. Vlaams Diergeneeskundig Tijdschrift. 2003;72:399408. 18. Gartrell CL, OHandley PA, Perry RL. Canine nasal diseasepart II. Compend Contin Educ Pract Vet. 1995;17:53947. 19. Burk RL. Computed tomographic imaging of nasal disease in 100 dogs. Vet Radiol Ultrasound. 1992;33:17780. 20. Saunders JH, van Bree h. Comparison of radiography and computed tomography for the diagnosis of canine nasal aspergillosis. Vet Radiol Ultrasound. 2003;44(4):41419. 21. Mathews KG, Koblik PD, Richardson EF, et al. Computed tomographic assessment of noninvasive intranasal infusions in dogs with fungal rhinitis. Vet Surg 1996;25(4):30919. 22. Boericke W. Aurum metallicum. In: Homoeopathic materia medica and repertory. New Delhi: B. Jain Publishers Pvt. Ltd; 1995:969. 23. Hering C. Aurum metallicum. In: The guiding symptoms of our materia medica. New Delhi: B. Jain Publishers, Pvt. Ltd; 1994:27091. 24. Epstein SR. Nasal aspergillosis treated homeopathically in a dog. J Am Hol Vet Med Assoc. 2006;25:916. 25. Hill PB, Hoare J, Lau-Gillard P, et al. Pilot study of the effect of individualised homeopathy on the pruritus associated with atopic dermatitis in dogs. Vet Rec. 2009;164(12):36470.

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