Tsunao Oh-i

The insulin ball

In August, 2005, a 62-year-old Japanese man, with a 20-year history of type 1 diabetes, was admitted to our hospital, for investigation of apparent insulin resistance. Since January, 2004, he had been taking insulin in a longacting (glargine) and a shortacting (lispro) form, at a total of 66 units a day. Despite the dose being gradually increased to 94 units a day, his blood glucose concen trations had subsequently been high, and poorly con trolled. Examination showed nothing of note. Blood tests gave a value for glycosylated haemoglobin (HbA1c) of 8∙6% (target value ≤6·5%). The patient’s body-mass index was 21∙1 kg/m2 (weight 57∙5 kg). Although we kept the patient on a strict diet, and increased the total daily dose of insulin to 116 units (lispro 94; glargine 22), his blood glucose concentration, before meals, remained 7∙8–21∙1 mmol/L. Blood tests showed normal concentrations of corticotropin, cortisol, thyroid hormones, glucagon, growth hormone, and carcino-embryonic antigen, and undetectable quantities of antibodies to insulin; urinary concen trations of meta nephrines were normal. Ultrasonography of the abdomen showed nothing of note. However, re-examination of the lower abdomen revealed two lumps, one on each side, under the skin; each contained a hard, irregular nodule, 3–4 cm in diameter. The patient had noticed the lumps several months previously; he routinely injected insulin into the nodules, since they were easily grasped, and injection was less painful than elsewhere. We admin istered insulin via a diff erent part of the abdomen; hypoglycaemia ensued. We rapidly decreased insulin doses. Good blood glucose concentrations were obtained with a total daily dose of 24 units (lispro 18; glargine 6). Abdominal MRI showed the nodules to lie in the fat under the skin; unlike fat, they had low signal intensity on T1-weighted (fi gure) and T2-weighted images. We took a biopsy sample of a nodule; histopathological analysis showed it to consist largely of amorphous, acellular, eosinophilic material. When the material was stained with Congo red, and seen with polarised light, we saw green birefringence, diagnostic of amyloid. On immunohistochemical testing, the amyloid deposit was positively stained by monoclonal antibodies to human insulin. When last seen, in November, 2008, the patient needed 66 units a day of insulin—injected outside the lumps, which were smaller than before. Common causes of insulin resistance include obesity; sever physical stress; prescribed drugs, such as glucocorticoids; and endocrine disorders, such as Cushing’s syndrome, phaeochromocytoma, or acromegaly. Rarer causes include mutations of the insulin receptor gene; antibodies to insulin, or to the insulin receptor; and lipodystrophy syndromes. Doctors should always consider if, and how, the patient is injecting insulin. Amyloid deposits consist of proteins arranged in a cross-β conformation: pathological amyloid deposits can be formed of various proteins, including α-synuclein in Parkinson’s disease, and prions in Creutzfeldt-Jakob disease. For amyloid to consist of insulin is rare. In all reported cases of insulin-induced amyloidosis, of which we are aware, the patient took non-human insulins: we speculate that aminoacid diff erences between endogenous and injected insulin may have contributed to the development of amyloidosis. Partly because use of nonhuman insulin is increasing, and partly because we have seen four cases recently, we speculate that insulininduced amyloidosis may be under diagnosed: for instance, by being mistaken for lipo hypertrophy. Injection into fatty lumps can reduce the eff ectiveness of insulin, though less markedly than does injection into amyloid. Amyloid lumps are typically harder, and more discrete, than fatty lumps of lipo hyper trophy; MRI can assist with diagnosis. We refer to amyloid lumps of insulin as “insulin balls”.

Changes in Plasma Serotonin Concentration and Acceleration Plethysmograms in Patients with Raynaud's Phenomenon after Long‐term Treatment with a 5‐HT2 Receptor Antagonist

High blood serotonin concentrations have been reported in patients with Raynauds phenomenon and a relationship has been suggested. Because of the difficulty in evaluating Raynauds phenomenon objectively, a possible correlation between blood serotonin concentrations and clinical findings has not yet been evaluated. We measured plasma serotonin concentrations and acceleration plethysmograms (APG) before and one year after administration of a serotonin receptor antagonist. Twenty‐seven patients with either collagen disease or diseases associated with Raynauds phenomenon were given a combined 5‐HT2 and serotonin receptor antagonist, sarpogrelate hydrochloride. Plasma serotonin concentrations were determined before and after administration and the APG d/a value was measured as an index of peripheral hemodynamics. These values were compared with the clinical symptoms of the patients. After one year of treatment, the subjective symptoms improved in 59.3% of patients who has Raynauds phenomenon. The pre‐treatment plasma serotonin concentrations of the study patients were significantly higher than those of the normal controls, but became significantly decreased following 5‐HT2 administration. However, there was no clear‐cut relationship with the clinical symptoms. The pre‐treatment APG d/a value of the patients was significantly lower than that of the normal controls, although there was no significant difference after administration when analyzed as an entire group or in a subset of patients whose symptoms did not subjectively improve or worsened after one year of treatment. In the subset in whom the subjective symptoms improved, however, the value significantly increased following administration, suggesting an improvement in peripheral hemodynamics. These results suggest the possibility that APG can be used as an objective index of peripheral hemodynamics.

Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series

OBJECTIVES Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption. METHODS Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients. RESULTS When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030). CONCLUSIONS Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.

Case of cutaneous Scedosporium apiospermum infection successfully treated with voriconazole

We report a case of cutaneous infection due to Scedosporium apiospermum in a 75‐year‐old immunocompromised male patient who had received long‐term corticosteroid and immunosuppressant therapy for the treatment of nephrotic syndrome. The patient came to our department complaining of erythema with a number of pustules on the dorsal surface of the right hand. S. apiospermum was identified from a culture taken from the pus. After unsuccessful treatment with topical ketoconazole, oral itraconazole and oral terbinafine, the lesion quickly resolved with the daily administration of 400 mg voriconazole. No recurrence was observed despite discontinuation of voriconazole due to drug‐induced hepatitis. Voriconazole holds out the promise of an effective treatment for invasive Scedosporium infection.

The occurrence of various collagen diseases in one family: a sister with ISSc, PBC, APS, and SS and a brother with systemic lupus erythematosus.

We encountered siblings who had collagen diseases and related symptoms. Case 1 was a 53‐year‐old woman who had limited cutaneous systemic sclerosis (ISSc) associated with primary biliary cirrhosis (PBC), antiphospholipid antibody syndrome (APS), and subclinical Sjögrens syndrome (SS). Case 2 was a 48‐year‐old man, her younger brother, with systemic lupus erythematosus (SLE) that developed at 32 years of age. Investigation of their family revealed that their mother had Raynauds phenomenon, arthritis, and subclinical Sjögrens syndrome, and that another younger brother of Cases 1 and 2 had Raynauds phenomenon and general fatigue. HLA analysis revealed that the sister and brother had some identical HLA antigens in common, including A2, A33 (19), B67, B44 (12), Cw7, DR2, DR6, DR52, and DQ1. The sister, brother and their mother had common HLA antigens including A2, B67, Cw7, DR2, and DQ1. Although Cases 1 and 2 shared the same HLA system, they presented different phenotypes of collagen disease.

Contact anaphylaxis due to para-aminophenol and para-methylaminophenol in hair dye

Case Report A 61-year-old man was being treated by his primary physician for eczema of the hands. The patient had been using a commercial hair dye about 1¿ a month for the previous 20 years. One day in May 2000, after using the hair dye, he began to develop upper airway stridor and generalized urticaria. The following month, while using the same hair dye (about 30–40 min after starting), the patient had dyspnea and generalized urticaria. He was evaluated in an emergency room, where the physician suspected anaphylaxis due to the hair dye. Open tests and prick tests with the hair dye (1% aq.) and its ingredients (para-phenylenediamine, paraaminophenol, ortho-aminophenol, para-methylaminophenol and sodium methyl oleoyl taurate) were all negative at 1%, 5% and 10% aq. Scratch tests with para-aminophenol (1%, 5% and 10% aq.) and para-methylaminophenol (1%, 5% and 10% aq.) were positive, using histamine dihydrochloride (1% aq.) as positive control and isotonic water as negative control. 10 control subjects also scratch tested with para-aminophenol and para-methylaminophenol were all negative. The patient was diagnosed as having a Type I allergy.

The relationship between angioblastoma (Nakagawa) and tufted angioma: report of four cases with angioblastoma and a literature-based comparison of the two conditions.

We report four recent cases of angioblastoma (Nakagawa). Histopathologic examinations of all cases revealed dispersed islets of clear marginal lobules of varying sizes in the dermis. Neoplastic endothelioid cells with moderate atypia and enlarged capillaries containing erythrocytes were found in the conglomerates. Recently, the features of this disease have been compared to the tufted angioma that has been reported in Europe and the U.S. Our evaluation suggests that these two diseases are very likely the same. We suggest that this disease should be called “angioblastoma” in agreement with the first report of this disease by Nakagawa.

Staphylococcal scalded skin syndrome in a healthy adult.

We report a case of staphylococcal scalded skin syndrome (SSSS) in a 65‐year‐old healthy woman. Fever, purulent conjunctivitis, and exfoliation of the skin in the gluteal region were noted. A scarlatiniform rash was observed on the body, and this erythema was followed by generalized desquamation. Staphylococcus aureus was isolated from her eye discharge, posterior nasopharynx, and the erosive surface of the skin. All the investigated strains produced exfoliative toxin B, but none produced toxic shock toxin‐1 (TSST‐1) or enterotoxin. The patient was treated with antibiotics and fluid supplementation, resulting in subsidence. This case is thought to have been caused by an abortive form of SSSS or a scarlatiniform variant, which is very rare in healthy adults.

A Case of Dermatomyositis Associated with Mechanic's Hand

A 67‐year‐old man was referred to the Department of Internal Medicine at Tokyo Medical University with interstitial pneumonia in July 1999. He presented with keratotic plaques on both palms and on the ventral and lateral sides of his fingers. Erythematous keratosis was observed on the dosal aspect of his fingers and metatarsophalangeal (MP) joints. Edematous erythema was seen on the patients chest, back, and the extensor surfaces of his arms. Electromyography revealed a myogenic pattern and an increased level of myogenic enzymes was found in the blood. Histological findings of the ventral sides of his fingers showed hyperkeratosis and parakeratosis of the dermal tissue and liquefaction degeneration of the basal layer at the papilla. Based on these findings, the patient was given a diagnosis of dermatomyositis associated with mechanics hand. A systemic examination confirmed interstitial pneumonia and carcinoma of the duodenal papilla. Mechanics hand is a type of dermatitis associated with myopathy first reported by Stahl et al. in patients with collagen disease. We report herein the first documented case of mechanics hand in Asians.

Perforating Pilomatricoma: Transepithelial Elimination or Not

We present a 56‐year‐old woman with a perforating pilomatricoma in the left eyebrow region. Histologically, the tumor consisted mainly of basophilic cells and shadow cells, and the tumor components were being eliminated through an ulcer with damage to the epithelial structures. In past reports of perforating pilomatricoma, this elimination pattern has often been described as transepithelial elimination. In many patients with perforating pilomatricoma, elimination is accompanied by ulceration and epithelial damage. Mehregan recently stated that elimination accompanied by epidermal necrosis and superficial ulceration constituted one form of transepithelial elimination. Epidermal necrosis and ulceration generally constitute severe damage. However, when Mehregan first proposed the concept of transepithelial elimination, it was defined as a phenomenon with relatively little or no damage to the epithelial structures, differentiating it from other types of elimination. This original definition makes transepithelial elimination a unique and interesting phenomenon, and its most important feature is that there is relatively little or no damage to the epithelial structures. Therefore, the terms “epidermal necrosis” and “ulceration” should not be used in association with transepithelial elimination. Hence, in patients with perforating pilomatricoma, the elimination of tumor components from ulcers with damage to the epithelial structures, as seen in the present case, should not be described as transepithelial elimination.