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Lowered plasma volume produces symptoms of postural hypotension Total body potassium loss and the general catabolism of muscle protein contribute to the weakness Paresthesias may be present at the time of diagnosis, particularly when the onset is subacute They reflect a temporary dysfunction of peripheral sensory nerves, which clears as insulin replacement restores glycemic levels closer to normal, suggesting neurotoxicity from sustained hyperglycemia When absolute insulin deficiency is of acute onset, the above symptoms develop abruptly Ketoacidosis exacerbates the dehydration and hyperosmolality by producing anorexia and nausea and vomiting, interfering with oral fluid replacement The patient s level of consciousness can vary depending on the degree of hyperosmolality When insulin deficiency develops relatively slowly and sufficient water intake is maintained, patients remain relatively alert and physical findings may be minimal When vomiting occurs in response to worsening ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep serum osmolality below 320 330 mosm/L Under these circumstances, stupor or even coma may occur The fruity breath odor of acetone further suggests the diagnosis of diabetic ketoacidosis Hypotension in the recumbent position is a serious prognostic sign Loss of subcutaneous fat and muscle wasting are features of more slowly developing insulin deficiency In occasional patients with slow, insidious onset of insulin deficiency, subcutaneous fat may be considerably depleted 2 Type 2 diabetes While many patients with type 2 diabetes present with increased urination and thirst, many others have an insidious onset of hyperglycemia and are asymptomatic initially This is particularly true in obese patients, whose diabetes may be detected only after glycosuria or hyperglycemia is noted during routine laboratory studies Occasionally, type 2 patients may present with evidence of neuropathic or cardiovascular complications because of occult disease present for some time prior to diagnosis Chronic skin infections are common Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women Diabetes should be suspected in women with chronic candidal vulvovaginitis as well as in those who have delivered large babies (> 9 lb, or 41 kg) or have had polyhydramnios, preeclampsia, or unexplained fetal losses Obese diabetics may have any variety of fat distribution; however, diabetes seems to be more often associated in both men and women with localization of fat deposits on the upper segment of the body (particularly the abdomen, chest, neck, and face) and relatively less fat on the appendages, which may be quite muscular Standardized tables of waist-to-hip ratio indicate that ratios of greater than 09 in men and greater than 08 in women are associated with an increased risk of diabetes in obese subjects Mild hypertension is often present in obese diabetics Eruptive xanthomas on the flexor surface of the limbs and on the buttocks and lipemia retinalis due to hyperchylomicronemia can occur in patients with uncontrolled type 2 diabetes who also have a familial form of hypertriglyceridemia.

monly in injection drug users Sinus infection may cause bony erosion Infection in subcutaneous tissues following traumatic implantation may develop as a well-circumscribed cyst or as an ulcer Nonpigmented septate hyphae are seen in tissue and are indistinguishable from those of Aspergillus when infections are due to S apiospermum or species of Fusarium, Paecilomyces, Penicillium, or other hyaline molds Spores or mycetomalike granules are rarely present in tissue Infection by any of a number of black molds is designated as phaeohyphomycosis These black molds (eg, Exophiala, Bipolaris, Cladophialophora, Curvularia, Alternaria) are common in the environment, especially on decaying vegetation Human disease due to these agents is rarely encountered but may result in soft tissue abscesses due to traumatic inoculation or may occur as a sequela of chronic sinusitis or profound immunosuppression In tissues of patients with phaeohyphomycosis, the mold is seen as black or faintly brown hyphae, yeast cells, or both Culture on appropriate medium is needed to identify the agent Histologic demonstration of these organisms is definitive evidence of invasive infection; positive cultures must be interpreted cautiously and not assumed to be contaminants in immunocompromised hosts Some isolates are sensitive to antifungal agents The differentiation of S apiospermum and Aspergillus is particularly important, since the former is uniformly resistant to amphotericin B but may be sensitive to azole antifungals (eg, voriconazole)

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Lamaris GA et al Scedosporium infection in a tertiary care cancer center: a review of 25 cases from 1989 2006 Clin Infect Dis 2006 Dec 15;43(12):1580 4 [PMID: 17109292] Raad II et al Posaconazole as salvage therapy for invasive fusariosis in patients with underlying hematologic malignancy and other conditions Clin Infect Dis 2006 May 15;42 (10):1398 403 [PMID: 16619151]

improved by the addition to itraconazole of flucytosine, 100 150 mg/kg/d by mouth divided into four doses Terbinafine at 500 mg/d may have similar efficacy to itraconazole Cryosurgery alone for smaller lesions or combined with itraconazole for larger lesions is beneficial

Esterre P et al Management of chromoblastomycosis: novel perspectives Curr Opin Infect Dis 2006 Apr;19(2):148 52 [PMID: 16514339]

MYCETOMA (MADUROMYCOSIS & ACTINOMYCETOMA)

Mycetoma is a chronic local, slowly progressive destructive infection, usually involving the foot, that begins in subcutaneous tissues, frequently after localized trauma, and then spreads to contiguous structures Maduromycosis (also known as eumycetoma) is the term used to describe mycetoma caused by the true fungi and by phylogenetically diverse organisms Actinomycotic mycetoma is caused by Nocardia and Actinomadura species The disease begins as a papule, nodule, or abscess that over months to years progresses slowly to form multiple abscesses and sinus tracts ramifying deep into the tissue Secondary bacterial infection may result in large open ulcers Radiographs may show destructive changes in the underlying bone Tissue Gram stain reveals fine branching hyphae with actinomycotic mycetoma Larger hyphae are seen with fungal mycetoma; the causative species can often be identified by the color of the characteristic grains within the infected tissues The prognosis is good for patients with actinomycetoma, since they usually respond well to sulfonamides and sulfones, especially if treated early TMP-SMZ, 160/800 mg orally twice a day, or dapsone, 100 mg twice daily after meals, has been reported to be effective Streptomycin, 14 mg/kg/d intramuscularly, may be useful during the first month of therapy All oral medications must be taken for months and continued for several months after clinical cure to prevent relapse Debridement assists healing The prognosis for maduromycosis is poor, though surgical debridement along with prolonged terbinafine or itraconazole therapy may result in a response rate of 70% The various etiologic agents may respond differently to antifungal agents, so culture results are invaluable Amputation is necessary in far advanced cases

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