Lecture 4 - Bacterial Skin Diseases I. NORMAL SKIN ENVIRONMENT A. Resident microflora Colonize normal skin and may be found in the superficial epidermis and hair follicles of normal skin. These commensal microflora play an important role in inhibiting colonization by pathogenic organisms. B. Skin infection: Pathogenic bacteria are causing clinical signs in the host. II. OVERVIEW OF PYODERMA A. Pathogenic bacteria: Staphylococcus intermedius is most common 1. Dog a. The primary skin pathogen is Staph. intermedius. In severe, complicated, or deep pyodermas, other organisms may also be causative (Pseudomonas, Proteus, etc.). b. Staphylococcus aureus and Staphylococcus schleiferi An increasing prevalence of Staph aureus and the emergence of a new species (Staph schleiferi) has been noted in dogs. Both species are pathogenic, have the ability to develop multidrug resistance, and are of zoonotic concern. 2. Cat Whereas bacterial skin infections are quite common in the dog, Staph pyodermas are uncommon in the cat. The most common skin infection in the cat is the bite wound abscess. B. Classification of pyoderma 1. Primary pyoderma: skin infection that occurs in healthy skin with no apparent cause. Uncommon. 2. Secondary pyoderma: skin infection that has an underlying cause or occurs in diseased skin. a. Most pyodermasare secondary in nature. b. Underlying causes: include allergies (approximately 80% of allergic dogs have a secondary pyoderma at time of diagnosis), mites, dermatophytes, seborrhea, and endocrine disorders. c. Diseased skin: trauma, moisture, immunocompromise, and altered normal flora predispose. 3. Depth of infection: pyodermas are characterized as surface, superficial, or deep (see later). C. Diagnosis 1. History and physical exam The diagnosis of pyoderma is made on exam based on clinical appearance of skin lesions. However, a meticulous history and complete physical exam is crucial in determining likely contributory causes (remember, most pyodermas are secondary!). 2. Basic tests used in the evaluation of all patients with pyoderma a. Thorough dermatologic exam: to evaluate for contributory causes. b. Skin scrapings: to look for mites. c. DTM culture: to evaluate for dermatophytes. d. Cytology (Diff-Quik): needle aspirate (of pustule, papule, nodule), or imprint of exudate. To evaluate for inflammatory cells (neutrophils, eosinophils) and microorganisms (bacteria, yeast, etc.). *Q: How can you differentiate between colonization and infection? Infection is associated with inflammatory cells and intracellular bacteria, colonization is not. 3. Tests pursued in deep, non-responsive, or recurrent pyodermas Skin biopsy: invaluable test in refractory, non-responsive pyoderma or dermatosis. i. Technique: obtain multiple skin biopsy samples (Baker biopsy punch often utilized). Collect intact primary lesions (ex: papule, vesicle) as well as samples with a border of normal:diseased skin. ii. Purpose: to obtain histopathologic diagnosis and look for causative etiology. b. Skin culture and sensitivity: to identify causative organism(s) and sensitivity pattern i. Biopsy: historically considered technique of choice (reduces likelihood of harvesting contaminants). The superficial skin is cleansed with an antiseptic and a punch biopsy is obtained and placed in a sterile vial containing transport media. ii. Skin swab: recent study (Evaluation of aerobic bacteriologic culture of epidermal collarette specimens in dogs with superficial pyoderma - JAVMA March 2005) indicates that swab technique was a simple and reliable method for identification of S. intermedius in dogs. c. Rule out contributory hypersensitivities *Q: How would you do this? d. Rule out underlying metabolic disease: CBC, profile, UA. e. Rule out underlying endocrine or immunologic disease: testing as indicated. D. Treatment of skin infections 1. Address underlying cause: key to successful treatment 2. Antibacterial shampoos a. Purpose Removes tissue debris and aids in eliminating bacteria in the more superficial layers of the skin (where antibiotic levels tend to be lower). b. Frequency of shampoo application: i. For active infections, provide shampoo therapy 2 - 3 times weekly. ii. For ongoing management, provide shampoo therapy 1 - 2 times weekly. Work up good lather and allow minimum of 10 - 15 minutes contact time. Most effective if hair is clipped short and washed first. c. Antibacterial shampoo options (see table) i. Benzoyl peroxide Most effective antibacterial shampoo. Also has keratolytic, antipruritic, degreasing and follicular flushing action. Can be irritating (drying) to the patient with inflamed or sensitive skin. Use of humectant spray or rinse after shampoo may be helpful. ii. Chlorhexidine Also an effective antibacterial shampoo that is less irritating for the patient with dry skin. Chlorhexidine is a good antiseptic (kills microbes on tissues) as well as disinfectant (kills microbes on inanimate objects). No degreasing activity, not keratolytic. iii. Ethyl lactate Similar to chlorhexidine in regards to efficacy. Antibacterial, rehydrating, keratoplastic, and has mild follicular flushing activity. iv. Other: sulfur containing shampoos (sulfur has both antibacterial and antifungal activity). d. Table of shampoos: adapted in part from: Practical Topical Therapy for Skin Infections Proceedings - WVC 2004 Karin M. Beale, DVM, DACVD Ingredients Shampoo Name Comments (K = keratolytic) Benzoyl Peroxide 2.5% Oxydex® DVM Deep pyoderma, folliculitis, can be drying, K Benzoyl Peroxide 3% Pyoben® Virbac As above, slow release formulation Benzoyl Peroxide 2.5%, Sulfur 2% SulfOxydex® DVM As above, also keratoplastic activity Benzoyl Peroxide 2.5% shampoo Micro Pearls Advantage Benzoyl Plus® EVSCO As above, also contains humectant Benzoyl Peroxide 2.5%, Sulfur 1 % Dermabenss® DermaPet As above, also contains humectant, Salicylic acid 1% Acetic acid 2%, Boric acid 2%, Malacetic® DermaPet Pyoderma, Malassezia, also in wipes, spray Chlorhexidine 2% shampoo ChlorhexiDerm® DVM Pyoderma Chlorhexidine 4% shampoo ChlorhexiDerm Maximum® DVM Pyoderma, Malassezia Chlorhexidine 2%, Sulfur Seba-Hex® EVSCO Pyoderma, Malassezia 2%, Salicylic acid2% Ethyl lactate10% Etiderm® Virbac Pyoderma, rehydrating, keratoplastic Ketoconazole 1%, Chlorhexidine 2% KetoChlor® Virbac Pyoderma, Dermatophytes, Malassezia Miconazole 2%, Chlorhexidine 2% Malaseb® DVM Pyoderma, Dermatophytes, Malassezia 3. Soaks and hydrotherapy (whirlpool bath) a. Purpose Helpful in the initial management of deep pyoderma to remove crusts and decrease surface bacteria. Clip hair in affected area, and apply soaks or whirlpools until drainage abates. b. Agents: dilute solutions of chlorhexidine or povidone-iodine are good antiseptics. 4. Topical antibacterial lotions, gels, wipes, spray: for localized lesions (table adapted from WVC 2004 Karin M. Beale DACVD) Product Ingredients Comments 1. Bactoderm ointment, Pfizer Mupirocin preferred topical antibiotic for Staph pyoderma 2. Malaseb wipes, Miconazole 2%, chlorhexidine 2% Pyoderma, DVM Dermatophytes, Malassezia 3. Resi-Chlor, Allerderm Chlorhexidine 2% lotion Localized pyoderma, Malassezia, Dermatophyte 4. Chlorhexiderm Maximum Chlorhexidine 4% spray Localized pyoderma, Malassezia, Dermatophyte 5. Gentocin spray, Gentamycin, betamethasone Schering 6. Tresaderm Merck Thiabendazole, dexamethasone, neomycin (neomycin less effective for pyoderma) 7. Oxydex gel, DVM 5% Benzoyl Peroxide gel 8. Silver Localized pyoderma with sulfadiazine cream Pseudomonas spp. 9. Polymixin B, Bacitracin Localized pyoderma, contains steroid (absorbed) Focal deep pyoderma, acne, can be drying Localized pyoderma with Pseudomonas spp. Inactivated by purulent exudates, Inactivated by purulent poor penetration exudates, poor penetration 5. Oral antibiotics a. Role Oral antibiotics are necessary to reach effective antibiotic levels in the skin in most pyodermas (as stratum corneum is a major barrier to effective topical penetration). b. Dose and duration of therapy i. Use maximal therapeutic dose Antibiotic levels in skin are often much less than that in blood. Must insure complete surface (look at) as well as deep (palpate) healing before discontinuing antibiotics. ii. First-time pyoderma Treat for minimum of 3 weeks (at least one week past clinical cure). iii. Complicated or deep pyoderma Typically treated for minimum of 8 weeks (at least 2 weeks past clinical cure). Early relapses (< 7 days) are likely due to inadequate initial treatment. Later relapses (weeks to months) or likely due to unresolved underlying cause. c. Selection of appropriate antibiotics (see table) i. First line antibiotics: used initially in the treatment of most superficial pyodermas. These antibiotics are typically narrow spectrum, preserve endogenous flora, and are effective against Staph intermedius (B-lactamase producer). ii. Second line antibiotics: used in recurrent, deep, or nonresponsive pyodermas. These antibiotics are often effective against resistant Staphylococcus and have an extended spectrum (to include gram negatives). Culture and sensitivity is best means by which to determine antibiotic selection. First line antibiotics Active ingredient Dose 1. Keflex® Cephalexin 30 mg/kg PO BID or 22 mg/kg PO TID 2. Cefa-Tabs® Cefadroxil 30 mg/kg PO BID or 22 mg/kg PO TID 3.Tribrissen® Trimethoprim/Sulfadiazine 30 mg/kg PO BID 4. Primor® Sulfadimethoxine/Ormetoprim 27.5 mg/kg BID for one day, then SID 5. Others Clindamycin, Erythromycin, Lincomycin Second line antibiotics Active ingredient Dose 1. Clavamox® Amoxicillin/Clavulanic acid 14 - 22 mgs/kg PO BID 2. Baytril® Enrofloxacin 5 - 10 mgs/kg PO BID 3. Simplicef® Cefpodoxime Proxetil 5 - 10 mg/kg PO SID 4. Zeniquin® Marbofloxacin2.75 5.5 mgs/kg PO SID 5. Orbax® Orbifloxacin 2.5 - 7.5 mg/kg SID **Important note: not all antibiotics noted above are approved for use in the cat. Consult drug insert prior to use. Significant side effects (and precautions) may be associated with use.** 6. Immunostimulation therapy May be helpful in the treatment of idiopathic recurrent pyoderma (no underlying causative factors identifiable). Staphage Lysate is a bacterialderived product given by injection (on a longterm basis - detailed protocol) and may help boost CMI to resolve pyoderma. Controversial benefit. III. SURFACE PYODERMAS A. Definition Bacterial colonization or overgrowth is present on the skin surface - but the skin is not infected. B. Intertrigo (skinfold pyoderma) 1. Etiology Occurs in breeds with excess skin folds and is due to irritation (skin rubbing against skin). Bacterial multiplication is encouraged by moisture, obesity, and secretions (urine, saliva). 2. Clinical signs a. Skin lesions occur in regions of the body with excessive folds and are characterized by local erythema, oozing, erosion, and odiferous discharge. b. Predisposed sites include lower lip (Spaniel, St Bernard), facial folds (brachycephalic breeds), vulvar fold (older obese female), tail fold (Pug, etc.) or body folds (Shar Pei). *Q: What may be another deleterious result of facial fold dermatitis? 3. Treatment: reduce obesity, antibacterial shampoos, topical antimicrobial products (mupirocin, Malaseb wipes, benzoyl peroxide gels) and surgical excision of excessive skin folds (if possible). IV. SUPERFICIAL PYODERMA A. Overview 1. Definition: bacterial infection of the skin that involves the epidermis and/or intact hair follicles. 2. Clinical lesions: can be variable Lesions often consist of papular to pustular eruptions (centered around the hair follicle), epidermal collarettes, and crusts. Many alternate clinical presentations also occur (see below). B. Impetigo (puppy pyoderma) 1. Clinical signs Mild superficial pustular rash and crusts in hairless inguinal and axillary region of young puppies (< 1 year). May be idiopathic or associated with dirty environment, poor nutrition, or parasitism. 2. Treatment Most cases are self-limiting and respond to topical antimicrobial shampoo therapy, systemic antibiotics are rarely needed. C. Bullous impetigo 1. Clinical signs Superficial pyoderma with large flaccid pus-filled bullae often noted in inguinal/axillary region. Occurs in adult dog and may be associated with underlying disease, immunosuppression (HAC, diabetes mellitus, etc). 2. Treatment: antimicrobial shampoo therapy, systemic antibiotics, look for cause. D. Superficial folliculitis: most common form of canine pyoderma (rare in cats) 1. Predisposing factors: most pyodermas are secondary. Staph intermedius is the primary cutaneous pathogen (other possible bacteria include E. coli , Proteus mirabilis, and Pseudomonas spp). Common predisposing conditions include demodicosis and dermatophytosis. 2. Clinical signs: lesions are variable a. Lesions Bacterial folliculitis = infection confined to hair follicle. The classic primary lesion is a tiny intact papule or pustule with a hair emanating from the center Lesions are often concentrated on the ventrum and trunk. b. Papulo-pustular rash May note papules, pustules, crusts, epidermal collarettes, and hyperpigmented or erythematous macules. c. Moth-eaten alopecia In other dogs, may note "surface bumps" covered by hair. Focal "moth-eaten" alopecia occurs as these hairs fall out. 3. Diagnosis: pursue appropriate tests (see above) - must answer question: Why is infection present? 4. Treatment a. Address underlying cause. b. Topical antibacterial (and sometimes anti-seborrheic) shampoo therapy (see table above). c. Oral antibiotics: institute therapy with a "first-line antibiotic." *Q: What is the minimum length of therapy? *Q: How do you determine when therapy is complete? Avoid concurrent use of glucocorticoids. d. Recurrence of disease: If pyoderma is pruritic and recurrent, consider underlying disease (*Q: Such as?). If pyoderma is recurrent and nonpruritic, consider other underlying diseases (*Q: Such as?) E. Pyotraumatic folliculitis (hot spot) 1. Etiology Peracute skin lesion caused by self-trauma that is triggered by a painful or pruritic event. 2. Clinical signs: most common in large breed, heavy coated dogs in warm humid climates. a. Initial lesions (pyotraumatic dermatitis) are well demarcated, painful, erythematous, moist, and have a yellowish center covered with a proteinaceous exuduate. Surface colonization of bacteria is present. b. Lesions rapidly progress to deeper involvement (pyotraumatic folliculitis) heralded by satellite papules and bacterial invasion of hair follicles. 3. Treatment a. Eliminate trigger, clip hair (may require sedation, lesions can be painful), and remove exudate with antibacterial shampoo. Elizabethan collar may be necessary. b. Topical antibacterial ointment (such as mupirocin): acts as a wound barrier and helps to address bacterial infection. c. Systemic therapy: first-line oral antibiotics for folliculitis (see above) and oral glucocorticoids at anti-inflammatory doses for 3 to 5 days to alleviate associated inflammation and pruritis. G. Juvenile cellulitis (juvenile pyoderma, puppy strangles) 1. Pathogenesis This is a sterile granulomatous and pustular disease of puppies that closely mimics superficial pyoderma. Cause unknown - may be heritable. 2. Clinical signs Acute swelling of the face and submandibular LN's followed by papules, pustules, oozing serum or pus, and crust formation. Systemic signs of illness are usually present. 3. Diagnosis: biopsies reveal granulomas and cellulitis, skin cultures are usually negative. 4. Treatment: immunosuppressive doses of glucocorticoids (most important), and oral antibiotics (to address secondary bacterial infection). V. DEEP PYODERMA A. Overview 1. Definition Skin infection is deeper and often serious, extending further down into the hair follicle, dermis or subcutis. May be associated with systemic signs of illness. Less common than superficial pyoderma. Rare in cat. 2. Pathogenesis Deep pyodermas do not occur spontaneously - they usually are a continuation of superficial pyoderma associated with underlying disease. 3. Skin lesions Several clinical syndromes exist, but characteristic lesions include red/purple nodules, hemorrhagic bullae, ulcerative lesions, and draining purulent fistulous tracts. a. Furunculosis: rupture of an infected hair follicle with release of keratin and bacteria in dermis, often associated with a pyogranulomatous response. b. Bacteria: Staph intermedius, and other potential invaders (Proteus spp, Pseudomonas, E. coli). c. Bacteremia and sepsis are potential systemic complications of deep pyoderma. 4. Treatment principles (applies to clinical syndrome's noted below) a. Identify and treat underlying disease (see above) b. Whirlpool soaks with antiseptic agents (where applicable) c. Antibacterial shampoos (particularly those shampoos with follicular penetration) d. Appropriate antibiotic therapy (second line antibiotic) for a minimum of 8 - 10 weeks and at least two weeks beyond clinical cure. e. Surgical excision of focal lesions, or debridement as indicated. f. Biopsy and culture (aerobic, anaerobic and fungal) should be pursued in all non-responsive cases. B. Localized forms of deep pyoderma 1. Callus pyoderma: occurs when calluses become secondarily infected. 2. Nasal folliculitis and furunculosis (nasal pyoderma) Painful, localized, deep infection of the nose found most often in German Shepherds and other dolichocephalic breeds. May be associated with "rooting" behavior. Uncommon. 3. Muzzle folliculitis and furunculosis (canine chin acne) a. Initial sterile inflammatory folliculitis that may progress to a deep bacterial furunculosis. Found most often in short-coated breeds. b. Follow treatment principles noted above. Local benzoyl peroxide shampoo and topical antibacterial therapy (such as mupirocin). 4. Acral lick furunculosis: infected lick granuloma Initial lesions often incited by boredom or other underlying trigger. Infected lesions are more likely to exhibit surface ulceration. 5. Pododermatitis (interdigital pyoderma) a. Clinical signs Painful, red, swollen feet with nodules and exudative draining fistulas. Variable pruritis, lameness, and lymphadenopathy. Males of shortcoated breeds are predisposed. b. Etiology: *Q: What other diseases may cause these signs? What if only one foot is affected? Bacterial infections are secondary - look for underlying cause (mites, FB's, allergies, etc.). Many cases are idiopathic. *What additional diagnostics should be pursued if only one foot is infected? C. Generalized forms of deep pyoderma 1. Deep folliculitis, furunculosis, and cellulitis. a. Clinical signs Note folliculitis, nodules, crusts, and open deep purulent fistulas with ulceration. Lesions may be found distributed over trunk, abdomen, and pressure points. b. Deep pyoderma of G. Shepherds i. Clinical signs as above but occurs in middle-aged German shepherd. Initial lesions frequently noted over rump and lumbosacral area. ii. Pruritis, regional lymphadenopathy, pain, and fever may be present. iii. Evaluate for underlying disease (particularly hypothyroidism, allergies, etc.) 2. Anaerobic cellulitis a. Deep suppurative infection within subcutaneous tissue planes often initiated by trauma or FB's, and secondary inoculation of microbes. Systemic illness, fever, crepitant cellulitis (gas-producing anaerobes), tissue discoloration and malodor may be present. b. Treatment: surgical debridement, antiseptic lavage and appropriate antibiotics. 3. Cat bite abscess (less common in dogs) a. Etiology i. Bite wound abscesses are most frequently noted in head or tail region. The skin seals over puncture site trapping bacteria inside, and abscess develops within 2 - 4 days (causative organisms are usually anaerobes from oral microflora). ii. Commmon inoculated oral microflora include Pasteurella multocida (also B-hemolytic Strep., Bacterioides, and Actinomyces spp.). b. Treatment Surgical debridement, antiseptic lavage, and appropriate antibiotics (penicillin, amoxicillin, cephalosporins for 1 - 2 weeks). *Q: How is this disease prevented? *Q: What other disease(s) may be transmitted by this behavior? VI. NODULAR DISEASES THAT MIMIC DEEP PYODERMA'S A. Overview 1. Clinical presentation a. Single to multiple cutaneous nodules are noted on exam. Some nodules may ulcerate and form fistulous tracts with draining exudate. b. Lesions are often indistinguishable from that due to the common bite wound abscess, sequestered foreign body, subcutaneous mycosis (see lecture 3), or isolated neoplasm. 2. Diagnostic evaluation a. Biopsy for histopathology and culture (aerobic, anaerobic, and fungal) to establish definitive diagnosis. Utilize special stains (fungal, mycobacterial) to ascertain causative etiology. b. Patients undergoing treatment for presumptive bite wound abscess should have biopsy/cultures performed if non-responsive to treatment. 3. Treatment a. For single lesions, surgical excision may be curative. b. For multiple lesions, specific antibiotic or chemotherapeutic protocols are often necessary (based on biopsy, culture/sensitivity results). B. Etiologic agents 1. Bacteria: may originate from the mouth (commensals) or soil (saprophytes). Organisms are typically inoculated into cutaneous wounds or traumatized skin. Causative agents include Actinomycosis and Actinobacillosis (oral microflora), and Nocardia (soil saprophyte). 2. Mycobacterial granulomas: caused by acid-fast mycobacteria a. True tuberculosis: rare disease in dogs and cats Usually due to infection with M. bovis or M. tuberculosis (obligate pathogens acquired by exposure to infected people, milk or meat). True tuberculosis is usually associated with systemic signs of illness (GI, respiratory disease) and treatment is not recommended due to zoonotic concerns. b. Feline leprosy (M. lepraemurium may be causative agent) Mode of transmission is unknown - insects may serve as vectors. c. Opportunist (atypical) mycobacterial infections These are saprophytes (M. fortuitum, M chelonei, others) found in the environment and likely introduced by wound contamination. Noted more often in the cat with lesions typically in ventral inguinal area. 3. Idiopathic sterile granuloma/pyogranuloma a. Etiology: suspected immune-mediated pathogenesis. Uncommon in dogs and rare in cats Lesions are characterized by firm, painless cutaneous nodules, plaques, or papules that sometimes ulcerate and drain. Secondary infection is uncommon. b. Treatment: surgical excision (solitary lesions), immunosuppressive doses of glucocorticoids (multiple lesions). Glucocorticoid therapy may need to be continued long-term. 4. Panniculitis: uncommon in dogs and cats Etiology: sterile inflammatory nodules of the subcutaneous fat - usually idiopathic. Lesions may ulcerate and drain an oily, yellowish-brown to bloody discharge. Multiple nodular form may be accompanied by fever and systemic signs. a. Treatment Surgical excision for solitary lesions and immunosuppressive doses of glucocorticoids for animals with multiple nodular form of disease. Anecdoctal reports suggest that oral cyclosporine (Atopica®) (in combination with glucocorticoids) is beneficial in treatment. Goals of Lecture 4 - Bacterial skin diseases References (for all dermatology lectures): Muller & Kirk's Small Animal Dermatology 5th edition 1995. Kirk's Current Veterinary Therapy XII. Bonagura. W.B. Saunders Co. 1996. WB Saunders Co. Selected excerpts from ACVIM 1995 and 1996 proceedings, and JAVMA, JIVM, and Compendium 1992-2006. Small Animal Dermatology Secrets: Karen L. Campbell 2004. Skin Diseases of the Dog and Cat Richard Harvey, Patrick McKeever 2003. Small Animal Dermatology A Color Atlas and Therapeutic Guide Linda Medleau, Keith Hnilica 2001 and Small Animal Ear Diseases An Illustrated Guide 2nd edition. Gotthelf 2005. Supplemental information also provided courtesy of Dr. Danny Scott and Dr. Miller, Cornell University. 1. What is the difference between resident microflora and pathogenic microflora on the skin? 2. What is the primary skin bacterial pathogen in the dog? How is the cat different? (A.2.) What is meant by a primary pyoderma? Secondary pyoderma? Which is more common? What underlying conditions predispose to development of pyoderma? (2.b.) 3. Be familiar with how to treat the patient with a pyoderma (D.1.2.) What shampoos are particularly effective? (c.i.ii.) When are oral antibiotics indicated? What type should be used? For how long? (5.a. b.i.ii. iii. C. i.ii.). What antibiotics are commonly used as first line agents? (Cephalosporins, Tribrissen). Second line agents? (Fluoroquinolones, Clavamox, Simplicef) 4. Be able to define surface, superficial and deep pyoderma. 5. Very briefly, be able to recognize and treat the following given a clinical description: patient with skin fold intertrigo, puppy pyoderma, hot spot (3.a.b.c.). 6. Be able to recognize and treat superficial folliculitis (know this disease) and briefly, how treatment is different for juvenile cellulitis (strangles) (4.) 7. Be familiar with information in V.A. 1.2.3.4. If given a clinical description, be able to recognize and treat the following forms of deep pyoderma (basic treatment principles as outlined in V.4.): callus pyoderma, muzzle folliculitis, interdigital pyoderma, generalized deep pyoderma, and cellulitis. 8. What are the clinical signs of the cat bite abscess? Likely causative organisms? Treatment recommendations? 9. What types of other nodular diseases may mimic the patient with a deep pyoderma? (VI. 1.b., atypical bacteria, mycobacteria, and panniculitis). What is the most effective diagnostic approach? (2.a.b.)