Dermatology , Dermatology Details

Dilemmas in Dermatology: Pearls & Pitfalls

Dilemmas in Dermatology: Pearls & Pitfalls
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Douglas J. DeBoer, DVM, Diplomate ACVD
University of Wisconsin

Certain skin diseases universally present diagnostic and/or treatment dilemmas for general practitioners and specialists alike, and opinions abound on the “best” way to handle these conditions. This uncertainty largely reflects our lack of knowledge about these skin diseases and our relative inability to make evidence-based statements.

This article presents 5 dermatologic conditions that raise plentiful questions, inspire a variety of opinions, and result in contentious discussion; often there is no one correct answer. The aim of the following presentations is to help you formulate your own approach to these dilemmas, and they are accompanied by key points on each topic, questions to be considered, and useful references for further study.

DILEMMA 1. I’ve diagnosed methicillin-resistant staphylococcal pyoderma. Now what?

Staphylococcal pyoderma is one of the most common dermatologic conditions in dogs. In addition, over the past 10 years, prevalence of antibiotic resistance in canine staphylococcal infections has substantially increased.1

If methicillin-resistant Staphylococcus (MRS) is present, the laboratory report will indicate that the organism is resistant to all beta-lactam antibiotics, including all penicillins and cephalosporins. Many strains of MRS are resistant to multiple classes of antibiotics, leaving the practitioner with few good options for treatment.

Clinical Pearls

The clinical pearl here is topical antiseptic therapy. We’re used to thinking of topical products as adjunct treatments (ie, used in addition to systemic antibiotics), but the thought process has changed. Now dermatologists are advocating that topical therapy be used instead of systemic antibiotic therapy in both resistant and nonresistant strains of Staphylococcus when possible.

Reducing systemic antibiotic use helps minimize risk for antimicrobial resistance. Topical antiseptic products kill even highly antibiotic-resistant strains. Most research in this area has been done with chlorhexidine, which is an excellent choice for topical therapy.2,3

Mild to moderate superficial pyoderma responds very well to daily topical application of 2% to 4% chlorhexidine (the percentage does not seem to matter), generally for 3 to 4 weeks (Figure 1). Key points are:

  • Medication must be applied daily.
  • To ensure daily application, provide the client with a spray, mousse, or other “leave-on” product to make frequent application easy for the client; whole-body chlorhexidine shampooing can still be done weekly.
FIGURE 1. Abdomen of a dog with papules, pustules, and epidermal collarettes indicative of superficial pyoderma. The treatment of choice for this localized disease is 2% to 4% chlorhexidine, applied once daily by spray, mousse, or other formulation, for 3 weeks or longer.

FIGURE 1. Abdomen of a dog with papules, pustules, and epidermal collarettes indicative of superficial pyoderma. The treatment of choice for this localized disease is 2% to 4% chlorhexidine, applied once daily by spray, mousse, or other formulation, for 3 weeks or longer.

More severe cases, or cases of deep pyoderma, still require systemic antibiotic treatment; choice of antibiotic is based on susceptibility results. It is particularly important to continue treatment until at least 2 weeks past complete clinical remission. Here, topical antiseptic treatment is a valuable adjunct therapy.

Pitfalls & Challenges

And the pitfalls? Among them, terminology and client education.

In dogs, MRS is usually Staphylococcus pseudintermedius (MRSP, an animal strain), but occasionally S schleiferi (MRSS, also of animal origin) or S aureus (MRSA, a human strain) is the culprit. It is important to get the species terminology and abbreviations correct; do not refer to these infections generically as “MRSA.”

A client using “MRSA” as an Internet search term will quickly become frightened by horror stories of human contagion. Instead:

  • Reassure clients that MRSP and MRSS are animal pathogens that are uncommonly transmitted to humans.
  • Point the client to websites with accurate, up-to-date information about MRS; one of the best is wormsandgermsblog.com.

For the practitioner interested in additional information about treating canine pyoderma, excellent reviews have been published recently.4,5

DILEMMA 2. What’s the best way to diagnose canine atopic dermatitis?

According to the current definition, canine atopic dermatitis (AD) is a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features, associated with immunoglobulin E (IgE) most commonly directed against environmental allergens.6

Pitfalls & Challenges

These environmental allergens include grass, tree, and weed pollens as well as molds and dust mites. This most recent definition allows that, in some individuals, the dermatitis may be triggered or exacerbated by other factors, such as food items. Additionally, it appears that some individuals with “atopic-like” clinical signs do not produce detectable allergen-specific IgE, illustrating the multifactorial pathogenesis of this condition.

For dogs with distinctly seasonal signs, diagnosis is not particularly difficult; the main rule out is seasonal occurrence of external parasites. For dogs with nonseasonal signs, however, making an accurate diagnosis can be challenging mainly because the most common clinical signs of AD are not pathognomonic. Numerous other skin conditions have overlapping signs. In addition, some dogs suffer from more than one allergic condition.

Clinical Pearls

In 2010, a prospective study that evaluated over 1000 pruritic dogs from 15 countries was published.7 In this study, AD was defined as cases with clinical features of atopic dermatitis irrespective of the offending agent. Clinical signs in dogs with AD were compared with signs observed in a group of dogs with pruritus from other causes, including fleas, scabies, other parasites, primary skin infections, and miscellaneous causes.

As a result of this study, new diagnostic criteria for AD were proposed (Table). A dog satisfying at least 5 of the 8 criteria has about an 80% chance of having AD. These criteria provide a useful and rapid screening method to identify potentially atopic dogs but must be used with some caution.

  1. The criteria are only an initial step; dogs fulfilling the criteria still must undergo diagnostic testing to rule out other conditions that can mimic AD.
  2. The criteria are focused on dogs with typical clinical signs of AD, and some dogs have atypical presentations. An 80% chance of being right also means a 20% chance of being wrong.
  3. Finally, 20% of dogs with clinical signs consistent with AD had food-induced signs that were indistinguishable from those of non–food-induced AD.

T1601C07Table
Most recently, subgroups of the International Committee on Allergic Diseases of Animals have published practical “white paper” reviews of current diagnostic methods and criteria for canine AD8 as well as updated treatment recommendations.9

DILEMMA 3. What is the best way to diagnose food allergy in dogs and cats?

Asking this question may be the single easiest way to start an argument among dermatologists. Food hypersensitivity is considered the third most common allergic condition diagnosed in dogs and cats after flea allergy and AD. It can be seen alone or in combination with these other allergies.

The controversies surrounding diagnosis of food allergy illustrate our inability to make evidence-based statements about this disease.

Pitfalls & Challenges

On clinical examination, there are no specific dermatologic signs that reliably differentiate food allergy from the other types of allergic disease (Figure 2). Clues to the presence of food allergy include:

  • History of year-round skin disease that does not always respond to standard anti-itch therapy, such as glucocorticoids
  • Presence of concurrent gastrointestinal signs (eg, mild or intermittent diarrhea, vomiting, flatulence)
  • Initial occurrence during puppyhood (though food allergy can occur at any age).
FIGURE 2. Pruritic abdominal/inguinal region in a dog with erythematous inflammatory allergic skin disease. Note the indication of chronic, low-grade inflammation as evidenced by the “lacy” hyperpigmentation pattern. It is impossible to distinguish via clinical signs whether the important allergens for this dog are environmental, food-related, or a combination thereof.

FIGURE 2. Pruritic abdominal/inguinal region in a dog with erythematous inflammatory allergic skin disease. Note the indication of chronic, low-grade inflammation as evidenced by the “lacy” hyperpigmentation pattern. It is impossible to distinguish via clinical signs whether the important allergens for this dog are environmental, food-related, or a combination thereof.

Clinical Pearls

The few things that experts are likely to agree on regarding food allergy are:

  • Serum allergy tests are not reliable for diagnosis. False-positive and false-negative results are common.
  • The only accurate test for food allergy is a carefully performed, strict, dietary restriction–provocation trial.
  • A diet trial must be performed for up to 3 months, although some animals experience relief much sooner.
  • Diet trials should never be performed with “pet store brand” diets, as these diets often contain trace amounts of important allergens not listed on the label.10

The most frequently asked question—“Which diet is the best to use?”—is the one that generates the most controversy. No convincing evidence exists regarding whether a home-cooked or commercially prepared diet is better for a given patient. Regardless of the diet chosen, compliance is paramount and strict adherence to the prescribed food is necessary.

Pearls & Pitfalls: Key Points

  1. Watch out for methicillin-resistant Staphylococcus (MRS) as a cause of canine pyoderma.
  2. To minimize development of antimicrobial resistance, treat dogs with mild to moderate superficial pyoderma with daily topical chlorhexidine, not antibiotics.
  3. Steer your clients to good sources of information on MRS, such as wormsandgermsblog.com.
  4. Diagnosis of canine atopic dermatitis is made using clinical criteria, not with an allergy test. For a recent review of clinical diagnosis, see reference 8; for up-to-date treatment recommendations, see reference 9.
  5. It is typically impossible to differentiate food allergy from other allergies based on clinical criteria alone. Serum testing for food allergy is unreliable; for correct diagnosis, use a dietary restriction–provocation trial.
  6. Early reports indicate that the isoxazoline compounds (afoxolaner and fluralaner) may be excellent treatments for canine generalized demodicosis. Stay tuned for more studies.
  7. Avoid long-term treatment of idiopathic feline eosinophilic granuloma complex diseases with injectable long-acting corticosteroids. Such use promotes both diabetes mellitus and treatment resistance. Instead, consider protocols using cyclosporine or chlorambucil.

DILEMMA 4. What’s best for treating canine generalized demodicosis?

Pitfalls & Challenges

Treatment options for canine demodicosis have been limited by lack of available products for treatment and potential adverse effects:

  • Amitraz is still a viable treatment option, although frequent dipping presents formidable compliance problems.
  • Oral ivermectin (0.4–0.6 mg/kg Q 24 H) is preferred by many, but adverse reactions (typically neurologic signs) can occur.
  • Milbemycin (1–2 mg/kg PO Q 24 H) is very effective and has recently reappeared on the U.S. market, but daily use makes it rather costly.
  • Topical once-weekly moxidectin + imidacloprid has met with variable success in the U.S.
  • Off-label use of doramectin (0.6 mg/kg SC once weekly) is sometimes considered, but may also produce adverse effects similar to those caused by ivermectin.

It is important for clients to understand that, regardless of the regimen selected, treatment must continue for a very long time—until repeated skin scrapings are negative—and, if treatment stops prematurely, the disease will surely return.

Clinical Pearls

This dilemma appears to be resolving, however, with the recent buzz about use of the isoxazoline compounds (afoxolaner and fluralaner) as off-label treatments for canine generalized demodicosis. There is only one published study of such use,11 but dermatologists are anecdotally reporting tremendous success with these drugs—even at the usual label-indicated, flea-and-tick prevention doses (Figure 3). More studies are sure to follow, and we may be on our way to an easy method for long-term control of this serious dermatosis.

FIGURE 3. Severe pododermatitis due to Demodex canis infestation in a dog before treatment (A). Two months after 2 monthly oral doses of afoxolaner, the dog showed marked improvement (B), which should continue with additional treatment.

FIGURE 3. Severe pododermatitis due to Demodex canis infestation in a dog before treatment (A). Two months after 2 monthly oral doses of afoxolaner, the dog showed marked improvement (B), which should continue with additional treatment.

DILEMMA 5. How should I treat feline eosinophilic granuloma complex?

Feline eosinophilic granuloma complex is a clinical syndrome that classically manifests as eosinophilic ulceration, eosinophilic plaque, or collagenolytic granuloma (Figure 4).

FIGURE 4. Eosinophilic granuloma disease (in this case, collagenolytic or “linear” granuloma) in a young cat. Although this pattern is usually thought to be a reaction to a parasite or allergen, some cases are idiopathic and may be treatment resistant.

FIGURE 4. Eosinophilic granuloma disease (in this case, collagenolytic or “linear” granuloma) in a young cat. Although this pattern is usually thought to be a reaction to a parasite or allergen, some cases are idiopathic and may be treatment resistant.

This syndrome should not be viewed as a specific diagnosis but rather as a reaction pattern in feline skin that may be induced by many different definable underlying causes, such as parasites, infection, or allergy. However, it is clear that feline eosinophilic granuloma complex can exist as an idiopathic condition on its own, without a definable cause. In such cases, initial treatment has often centered on long-acting injectable glucocorticoids, such as methylprednisolone acetate. When the disease is idiopathic and recurrent, problems arise when:

  1. Each glucocorticoid injection makes development of diabetes mellitus more likely or
  2. The disease is, or becomes, glucocorticoid resistant.

Other treatment protocols include those based on:

  • Cyclosporine: May need to be used at doses up to 13.3 mg/kg PO Q 24 H12 or
  • Chlorambucil: 0.1–0.2 mg/kg PO Q 24 H or Q 48 H.13

Exercise caution with these protocols: this dose of cyclosporine is nearly twice the feline label dose of 7 mg/kg, and possibility of adverse effects is increased, while chlorambucil is a potent and potentially myelosuppressive drug. Monitoring cyclosporine levels and complete blood counts may be advisable in some cases.

The treatments outlined are not always effective, however, and it appears that this dilemma may persist for some time to come.

AD = atopic dermatitis; IgE = immunoglobulin E; MRS = methicillin-resistant Staphylococcus; MRSA = methicillin-resistant Staphylococcus aureus; MRSP = methicillin-resistant Staphylococcus pseudintermedius; MRSS = methicillin-resistant Staphylococcus schleiferi

To learn more about the dermatologic conditions discussed in this article, read the following articles available at tvpjournal.com:

  • What is New in the Diagnosis and Management of Canine Atopic Dermatitis? (May/June 2015)
  • Treating Resistant Skin Infections in Dogs (May/June 2014)
  • Feline Dermatology: Cats Are Not Small Dogs (November/December 2013)
  • My 6-Step Plan for Diagnosing & Managing the Pruritic Dog (July/August 2013)
  • Methicillin-Resistant Staphylococcal Infections: Recent Developments (May/June 2013)
  • Challenges & New Developments in Canine Pyoderma: Disease Overview & Diagnosis (January/February 2012) and Topical & Systemic Treatment (March/April 2012)

 

References

  1. Jones RD, Kania SA, Rohrbach BW, et al. Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772 samples (2001-2005). JAVMA 2007; 230:221-227.
  2. Borio S, Colombo S, La Rosa G, et al. Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: A randomized, blinded, antibiotic-controlled study. Vet Dermatol 2015; doi: 10.1111/vde.12233.
  3. Clark SM, Loeffler A, Bond R. Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: Opportunities for topical therapy of canine superficial pyoderma. Vet Rec 2013; 172(6):156-160.
  4. Beco L, Guaguere E, Mendez L, et al. Suggested guidelines for using systemic antimicrobials in bacterial skin infections: Part 2—antimicrobial choice, treatment regimens and compliance. Vet Rec 2013; 172:156-160.
  5. Hillier A, Lloyd DH, Weese JS, et al. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Vet Dermatol 2014; 25:163-175, e42-e43.
  6. Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol Immunopathol 2006; 114:207-208.
  7. Favrot C, Steffan J, Seewald W, et al. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Vet Dermatol 2010; 21:23-31.
  8. Hensel P, Santoro D, Favrot C, et al. Canine atopic dermatitis: Detailed guidelines for diagnosis and allergen identification. BMC Vet Res 2015; 11:196.
  9. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res 2015; 11:210.
  10. Okuma TA, Hellberg RS. Identification of meat species in pet foods using a real-time polymerase chain reaction (PCR) assay. Food Control 2015; 50:9-17.
  11. Fourie JJ, Liebenberg JE, Horak IG, et al. Efficacy of orally administered fluralaner (Bravecto) or topically-applied imidacloprid/moxidectin (Advantage) against generalized demodicosis in dogs. Parasites Vectors 2015; 8:187.
  12. Vercelli A, Raviri G, Cornegliani L. The use of oral cyclosporin to treat feline dermatoses: A retrospective analysis of 23 cases. Vet Dermatol 2006; 17:201-206.
  13. Buckley L, Nuttall T. Feline eosinophilic granuloma complex(ities): Some clinical clarification. J Feline Med Surg 2012; 14:471-481.

Author_D-DeBoerDouglas J. DeBoer, DVM, Diplomate ACVD, is a professor of dermatology at University of Wisconsin—Madison School of Veterinary Medicine. Dr. DeBoer received his DVM at University of California—Davis and completed postgraduate training at Michigan State University and at University of California—Davis. Dr. DeBoer is a frequent lecturer at national and international continuing education courses for graduate veterinarians. His research and clinical interests include the immunology of recurrent and chronic skin diseases, with a focus on canine allergic skin disease.

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>Bahrain</option><option value='Bangladesh' >Bangladesh</option><option value='Barbados' >Barbados</option><option value='Belarus' >Belarus</option><option value='Belgium' >Belgium</option><option value='Belize' >Belize</option><option value='Benin' >Benin</option><option value='Bermuda' >Bermuda</option><option value='Bhutan' >Bhutan</option><option value='Bolivia' >Bolivia</option><option value='Bonaire, Sint Eustatius and Saba' >Bonaire, Sint Eustatius and Saba</option><option value='Bosnia and Herzegovina' >Bosnia and Herzegovina</option><option value='Botswana' >Botswana</option><option value='Bouvet Island' >Bouvet Island</option><option value='Brazil' >Brazil</option><option value='British Indian Ocean Territory' >British Indian Ocean Territory</option><option value='Brunei Darussalam' >Brunei Darussalam</option><option value='Bulgaria' >Bulgaria</option><option value='Burkina Faso' >Burkina Faso</option><option value='Burundi' >Burundi</option><option value='Cambodia' >Cambodia</option><option value='Cameroon' >Cameroon</option><option value='Canada' >Canada</option><option value='Cape Verde' >Cape Verde</option><option value='Cayman Islands' >Cayman Islands</option><option value='Central African Republic' >Central African Republic</option><option value='Chad' >Chad</option><option value='Chile' >Chile</option><option value='China' >China</option><option value='Christmas Island' >Christmas Island</option><option value='Cocos Islands' >Cocos Islands</option><option value='Colombia' >Colombia</option><option value='Comoros' >Comoros</option><option value='Congo, Democratic Republic of the' >Congo, Democratic Republic of the</option><option value='Congo, Republic of the' >Congo, Republic of the</option><option value='Cook Islands' >Cook Islands</option><option value='Costa Rica' >Costa Rica</option><option value='Côte d&#039;Ivoire' >Côte d&#039;Ivoire</option><option value='Croatia' >Croatia</option><option value='Cuba' >Cuba</option><option value='Curaçao' >Curaçao</option><option value='Cyprus' >Cyprus</option><option value='Czech Republic' >Czech Republic</option><option value='Denmark' >Denmark</option><option value='Djibouti' >Djibouti</option><option value='Dominica' >Dominica</option><option value='Dominican Republic' >Dominican Republic</option><option value='Ecuador' >Ecuador</option><option value='Egypt' >Egypt</option><option value='El Salvador' >El Salvador</option><option value='Equatorial Guinea' >Equatorial Guinea</option><option value='Eritrea' >Eritrea</option><option value='Estonia' >Estonia</option><option value='Eswatini (Swaziland)' >Eswatini (Swaziland)</option><option value='Ethiopia' >Ethiopia</option><option value='Falkland Islands' >Falkland Islands</option><option value='Faroe Islands' >Faroe Islands</option><option value='Fiji' >Fiji</option><option value='Finland' >Finland</option><option value='France' >France</option><option value='French Guiana' >French Guiana</option><option value='French Polynesia' >French Polynesia</option><option value='French Southern Territories' >French Southern Territories</option><option value='Gabon' >Gabon</option><option value='Gambia' >Gambia</option><option value='Georgia' >Georgia</option><option value='Germany' >Germany</option><option value='Ghana' >Ghana</option><option value='Gibraltar' >Gibraltar</option><option value='Greece' >Greece</option><option value='Greenland' >Greenland</option><option value='Grenada' >Grenada</option><option value='Guadeloupe' >Guadeloupe</option><option value='Guam' >Guam</option><option value='Guatemala' >Guatemala</option><option value='Guernsey' >Guernsey</option><option value='Guinea' >Guinea</option><option value='Guinea-Bissau' >Guinea-Bissau</option><option value='Guyana' >Guyana</option><option value='Haiti' >Haiti</option><option value='Heard and McDonald Islands' >Heard and McDonald Islands</option><option value='Holy See' >Holy See</option><option value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' >Zimbabwe</option></select> <label for='input_6_10_6' id='input_6_10_6_label' 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