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What's Your Diagnosis? Reacting to multifocal skin nodules DIAGNOSIS By Louis-Phillippe de Lorimier,SĂƒÂŠbastien Kfoury,Tanya Higgins The main differential diagnoses were: cutaneous reactive histiocytosis multiple histiocytomas multifocal cutaneous malignancy (mast cell tumors, cutaneous lymphoma, plasma cell tumors) infectious diseases (deep bacterial folliculitis/furunculosis, dermatophytic granulomas, systemic mycoses), and immune-mediated diseases (idiopathic sterile nodular panniculitis, multifocal granulomatous inflammation). Two incisional biopsies (6 mm punch) were obtained for histopathologic analysis, and cephalexin was prescribed at 19 mg/kg BW, PO, q12h pending biopsy results. Histopathology confirmed a severe, nodular, lymphohistiocytic dermatitis most compatible with cutaneous reactive histiocytosis. Hematology and a chemistry profile were performed and all results were within the reference range. Other diagnostic tests were recommended (thoracic and abdominal imaging) but declined. Tetracycline was started at 500 mg PO, q8h, and combined with over-the-counter niacinamide at the same dosage and frequency, for long-term administration. On recheck examination 6 weeks later, the cutaneous lesions were 90% improved, though some were still present on the right flank. Essential fatty acids were added to the treatment regimen (AllerG-3, Vet Solutions). After another 6 weeks, the lesions had all resolved and the frequency of tetracycline/niacinamide administration was decreased to twice daily. Finally, another 6 weeks later (18 weeks following diagnosis), the dog was still free of detectable lesions and the frequency of administration was decreased to once daily. At the time of this writing, he has been treated with once daily administration for 6 weeks, and is still free of cutaneous lesions. Discussion There are many histiocytic proliferative disorders, classified as neoplastic or nonneoplastic based on their biological behavior and cell lineage as identified with specific immunomarkers.1-3 The neoplastic histiocytic disorders include the benign cutaneous histiocytoma, localized histiocytic sarcoma, and disseminated histiocytic sarcoma (previously known as malignant histiocytosis), while the nonneoplastic disorders include cutaneous histiocytosis (CH) and systemic histiocytosis (SH).1-3 Benign cutaneous histiocytomas generally present as a solitary, round and firm, raised and erythematous lesion, rarely larger than 2 cm in diameter, most commonly observed in young dogs, typically before 3 to 4 years of age, on the cranial half of the body (Figure 3). They originate from intraepidermal antigen-presenting cells (Langerhans cells).1-3 They may grow rapidly (1 to 4 weeks), and the vast majority will thereafter regress spontaneously following T-cell infiltration, generally over 1 to 2 months.1-3 Histiocytic sarcoma is an aggressive, malignant tumor of dendritic cell origin that can present with a localized or disseminated form at diagnosis. Overrepresented breeds include the Bernese mountain dog, the golden retriever, the rottweiler, and the flat-coated retriever. 1,2,4 Multiple organs can be involved including large joints (elbow, stifle), lymph nodes, skin, spleen, liver, lungs (Figure 4), and bone marrow.1-4 The overall prognosis is guarded, especially when disseminated at diagnosis, but clinical responses are observed with standard cancer therapy including surgery 1,2,4 (localized form), radiation therapy, and systemic chemotherapy. Two diseases are nonneoplastic and described as reactive histiocytoses: cutaneous histiocytosis, and systemic 1-3,5 5 histiocytosis. Both reactive histiocytic disorders are the result of activated (nonneoplastic) dermal dendritic cells. SH is more frequently diagnosed in Bernese mountain dogs, rottweilers, golden and Labrador retrievers, and Irish wolfhounds.1-3,5 With SH, many organs can be affected with lesions, including the skin and subcutis, lymph nodes,

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bone marrow, scrotum, spleen, liver, lung, and mucous membranes.1-3,5 Affected dogs are most typically young to middle-age (3 to 9 years of age on average), and clinical signs, which can include depression, anorexia, weight loss, conjunctivitis, and difficult breathing, may wax and wane.1,2 Certain clinicopathologic changes, such as anemia, 1 monocytosis, and lymphopenia, are frequently reported. Various therapies have been described, most typically involving the use of immunosuppressive agents, but prospective studies are needed.1-3,5 CH tends to occur in young to middle age dogs (median 4 years in recent study), has no known breed predisposition, and a male predilection has been described.1-3,5,6 Contrary to SH, lesions of CH are limited to the skin and subcutis, with commonly reported sites including the head, pinna, nasal planum/nares, limbs, and scrotum.1-3,5,6 The lesions, as in the case discussed here, are typically haired or alopecic erythematous plaques or nodules. Nasal planum lesions may give a typical "clown nose" appearance.1-3,5,6 Similar to SH, lesions may wax and wane, and progression from CH to SH has been described. 5 Until recently, there were few reports regarding therapeutic options for dogs with CH. A recent retrospective study described 32 cases of CH treated with various therapies.6 That study was the first one to report on the use of tetracycline and niacinamide (+/- vitamin E and/or essential fatty acids), and concluded that it was an effective treatment option for dogs with CH, though patients with nasal planum lesions suffered a higher risk for recurrence.6 Though many dogs of that study responded to other forms of therapy (mainly corticosteroids and other immunosuppressants), the authors recommended niacinamide and tetracycline 6 maintenance therapy to possibly decrease the risk of recurrence. Dosages used in that study were 250 mg of each drug three times daily for dogs weighing less than 10 kg and 500 mg three times daily for dogs weighing more than 10 kg. 6 References 1. Clifford CA, Skorupski KA. Histiocytic diseases. In Withrow SJ, Vail DM (eds): Small Animal Clinical Oncology, ed 4. Elsevier, St. Louis, Mo., 2007. 2. Coomer AR, Liptak JM. Canine histiocytic disorders. Compend Contin Educ Vet 2008;30:202-217. 3. Angus JC, de Lorimier LP. Lymphohistiocytic neoplasms. In Campbell KL (ed): Small Animal Dermatology Secrets. Hanley & Belfus, Philadelphia, 2004. 4. Skorupski KA, Clifford CA, Paoloni MC et al. CCNU for the treatment of dogs with histiocytic sarcoma. J Vet Intern Med 2007;21:121-126. 5. Affolter VK, Moore PF. Canine cutaneous and systemic histiocytosis: reactive histiocytosis of dermal dendritic cells. Am J Dermatopathol 2000;22:40-48. 6. Palmeiro BS, Morris DO, Goldschmidt MH, Mauldin EA. Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases. Vet Dermatol 2007;18:332-240.

Reacting to multifocal skin nodules