Cytokines and growth factors in keratinocytes and sweat glands in chronic venous leg ulcers. An immunohistochemical study

The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing.     

With this eruption, there is not a second to lues

A 28-year-old white man presented to the Emergency Department with a 24-hour history of an eruption on his extremities, trunk, and face. The patient was known to be HIV positive with a CD4 count of 527 and a viral load of 20,300. He denied fever, chills, malaise, and headache. His social history was significant for the fact that he was in a monogamous homosexual relationship. He had no recent travel, pet exposures, or sick contacts. Physical examination revealed stable vital signs and no documented fever. A maculopapular eruption was present on his face, trunk, and extremities (Figures 1 and 2). There was no palmar or plantar involvement. He was treated with diphenhydramine and topical 2.5% hydrocortisone and advised to return if his condition did not improve. Twelve days after the initial evaluation, the patient consulted us again due to progression of his dermatitis. He had no additional complaints other than an eruption on both palms but neither sole. (Figure 3). The eruption now demonstrated erythematous pink-red oval macules and papules 1-2 cm in size distributed on his scalp, face, trunk, and arms. A few papules contained fine collarettes of scale. Further questioning revealed that the patient had experienced a tender rectal ulcer 2 months previously. A punch biopsy and rapid plasma reagin were performed. The histopathologic examination revealed interface dermatitis with lymphocytes, plasma cells, occasional neutrophils, and a prominent lymphoplasmacytic perivascular dermatitis with infiltration of the vessel walls. Warthrin-Starry and Steiner methods demonstrated spirochetes at the dermal-epidermal junction and in vessel walls, consistent with Treponema pallidum (Figure 4). Rapid plasma reagin and fluorescent Treponema antibody were both reactive with a Venereal Disease Research Laboratory (VDRL) of 1:16. The patient was diagnosed as having secondary syphilis and treated with 2.4 million units of IM benzathine penicillin for 3 weeks. His eruption resolved after the initial treatment and he did not experience a Jarisch-Herxheimer reaction.     

Necrotic ulcer: a manifestation of leukemia cutis

A 71-year-old man presented to our dermatological clinic with a 3-month history of a wound on his leg. He complained of weakness for the past few months. On his dermatological examination he had a 3x3-cm necrotic ulcer on his left tibia (Figure 1). On physical examination, there was 1 x 1-cm axillary lymphadenopathy. There was no other lymph node enlargement, hepatosplenomegaly, or gingival hypertrophy. Peripheral blood results showed 2.4x103/mm3 leukocytes (normal range 4-11 x 103/mm3) with 66% neutrophils. The hemoglobin value was 10.1 g/dL (13-18 g/dL), and the platelet count was 63x103/mm3 (150-440 x 103/mm3). No blasts were detected in a peripheral blood smear. His lactate dehydrogenase level was 567 U/L (240-480 U/L). All other results of blood chemistry were within normal limits. Punch biopsy of the skin lesion showed ulceration and dense dermal acute and chronic inflammation. There was a superficial and deep perivascular and periadnexal infiltrate of neoplastic cells composed of relatively abundant eosinophilic cytoplasm and large nuclei with blastic chromatin and occasional small nucleoli (Figure 2). Mitotic figures were prominent. Immunohistochemical stains were performed, and the neoplastic cells were CD3, CD20, CD138, and S100 protein negative. Myeloperoxidase and CD68 were positive. The histopathological findings were consistent with leukemic infiltration. Examination of bone marrow biopsy revealed that the blastic cells constituted more than 20% of the bone marrow cellularity. Cytogenetic analysis of bone marrow aspiration with fluorescence in situ hybridization was negative for inversion 16, t(8;21) and t(15;7). Histochemical stains for myeloperoxidase, sudan black, periodic acid-Schiff, and alpha naphthyl acetate were also negative. Blastic cells were DR, CD13, CD117, and CD34 positive and CD5, CD7, CD10, CD14, CD19, CD20, CD33, CD41, CD56, CD64, and CD79 negative according to flow cytometry immunophenotyping. Blastic cells were 35% in the bone marrow. Based on the findings of bone marrow examination, the patient was diagnosed as having acute myeloblastic leukeamia (AML) with minimal differentiation (subtype MO) according to French-American-British and World Health Organization classification. The examination of abdominal ultrasonography and thorocic and abominal computed tomography revealed no metastases. The patient was treated with chemotherapy that consisted of cytarabin and daunorubicin. After chemotherapy, the lesion regressed. One month after chemotherapy, the patient presented to the hospital with a complaint of fever. He was diagnosed with febrile neutropenia. He died of cardiac failure 12 months after appearance of skin infiltration.     

Familial juvenile generalized pustular psoriasis: response to methotrexate

Two siblings with generalized pustular psoriasis were admitted to the hospital. Case 1: A 7-year-old girl presented with recurrent episodes of multiple pinhead-sized pustules all over her body since the age of 3. The current episode began a week prior to the onset of the lesions. On cutaneous examination, she had generalized erythema topped with tiny pustules, scales, and crusting (Figure 1A). A Gram stain performed from the pustule and cultures taken from the pus and blood were sterile. Histopathology of the pustule was suggestive of pustular psoriasis (Figure 2). Hemoglobin was 8.8 g%. Other hematologic, microbiologic, and radiologic investigations were normal. Treatment was started with methotrexate, to which she responded dramatically with reduction in appearance of new lesions, erythema, and scaling. After 4 weeks of treatment, there was almost 90% clearance of skin lesions. Case 2: A 3-year-old boy, brother of the patient in case 1, presented with similar complaints for the past week. The episode was preceded by high-grade fever. He had generalized erythema, scaling, and edema and multiple pinhead-sized pustules, some of which were arranged in an annular configuration (Figure 1B). All investigations, as in case 1, were normal except for hypocalcemia (Ca2+ = 8.8 g%) and generalized rarefaction on x-rays of both the ankle joints. Treatment was started with prednisolone (because of poor general condition) and methotrexate. Following therapy, significant improvement was evident with reduction in erythema and cessation of appearance of new pustules. The dose of prednisolone was gradually tapered after 3 weeks and then stopped.     

Basal cell carcinoma is not granulation tissue in the venous leg ulcer

The authors present a case of a 76-year-old female with a 7-year history of a nonhealing leg ulcer. The wound surface had epithelial tissue present in a diffuse way with shiny granulations on parts of the edge of the ulcer. A biopsy of the ulcer edge was performed to study the reasons for the absence of response to treatment and the presence of abnormal granulation tissue. The result showed the presence of a basal cell carcinoma. The authors conclude that skin biopsy is very important in nonhealing chronic venous ulcers because carcinomas may mimic granulation tissue and complicate venous ulcers.     

An unusual cutaneous manifestation of Crohn's disease

A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without organisms. Tissue cultures were negative for bacterial, fungal, and mycobacterial infection. Skin biopsy taken from the central upper back demonstrated subcorneal pustules with areas of eroded epidermis and collections of neutrophils in the superficial dermis (Figure 3). Special stains were negative for organisms. He received infliximab infusion 5 mg/kg for a total dose of 420 mg over 2 hours. Within 48 hours of infusion, there was notable decrease in size of lesions, in addition to reduction of purulent drainage from both eyes. The patient was discharged home following infliximab infusion. His skin lesions resolved during a period of 2 weeks, leaving small pink atrophic scars. He received his second infusion of infliximab 2 weeks after discharge with continued improvement in his gastrointestinal symptoms.     

Psoriasis triggered by mefloquine

A 46-year-old Caucasian man living on the central Mediterranean island of Gozo (Malta) was started on mefloquine 250 mg once weekly before a trip to lower Egypt. He took his medication 1 week before starting his holiday and was advised to continue it for 4 weeks after returning. He did not take any other medication and enjoyed the holiday, which he initially intended to repeat in the near future. His medical history revealed a number of episodes of psoriasis for which he sought dermatologic advice. He had been given systemic therapy on at least one occasion, but the condition had been fairly quiescent for some time and he had not needed to consult a dermatologist for more than 4 years. Soon after the third tablet of mefloquine and effectively just after his return home to Gozo, the patient noticed that the psoriasis was "creeping back." He noted progressive deterioration in his skin problem but nevertheless finished the recommended course of therapy considering that "being sure about not developing malaria was far more important than a touch of psoriasis." The psoriasis worsened to the extent that he had taken off work for 2 weeks from his job as a self-employed carpenter at the time of referral. On examination, clearly there was a significant flare up of his psoriasis with severe involvement of the hands (Figure 1) and feet and less so over the rest of his body. He had been off work and matters were steadily getting worse in spite of topical treatment with a combination of calcipotriol-betamethasone ointment. Oral methotrexate 15 mg once weekly was commenced together with topical therapy with good results (Figure 2).     

A pilot clinical study of hair grafting in chronic leg ulcers

Epidermal sheets spread centrifugally postinjury from the hair follicle infundibulum to reepithelialize the wound bed. Healing progresses faster in skin areas rich in terminal hair follicles. These observations are consistent with the role of the hair follicle as a major reservoir for progenitor cells. To evaluate the feasibility and potential healing capacity of autologous scalp follicular grafts transplanted into the wound bed of chronic leg ulcers, 10 patients with ulcers of an average 36.8 cm² size and a 10.5‐year duration were included in this pilot study. Within each ulcer we randomly assigned a 2 × 2 cm “experimental” square to receive 20 hair grafts and a nongrafted “control” square of equal size. The procedure seemed to be safe, although major unrelated complications occurred in two patients. At the 18‐week end point, we observed a 27.1% ulcer area reduction in the experimental square as compared with 6.5% in the control square (p = 0.046) with a maximum 33.5% vs. 9.7% reduction at week 4 (p = 0.007). Histological analyses showed enhanced epithelialization, neovascularization, and dermal reorganization. We conclude that terminal hair follicle grafting into wound beds is feasible in an outpatient setting and represents a promising therapeutic alternative for nonhealing chronic leg ulcers.     

Dermatofibroma on the palmar surface of the hand

Case 1: A 58-year-old man presented with a solitary asymptomatic nodule on his thumb (Figure A). After trauma with a rusty nail approximately 20 years ago, he had developed a small papule, which had enlarged gradually for a few days initially before stabilizing. His personal and family medical histories were unremarkable. Dermatologic examination revealed a 1-cm crater-like nodule on the left palmar area. This was a firm and nontender lesion that was fixed to the overlying skin but moved freely from underlying structures. There were no similar lesions elsewhere on his body. Case 2: A 52-year-old man presented with a nodular lesion on the left palmar surface of his thumb. The 0.8-cm lesion was lightly colored, with a central cup-shaped epidermal depression and thin epidermis. The patient described an insect bite to the area 15 years earlier as the precipitating event. The firm and nontender lesion was fixed to the overlying skin but moved freely from underlying structures (Figure B). Case 3: A 36-year-old man consulted for a nodular lesion, located on his left palmar surface, that had not enlarged or changed since appearing 3 years ago. He described mechanical trauma to the area as precipitating the lesion. Clinical examination revealed a 0.6-cm, well-circumscribed nodule, with a dome shape and colored skin. Clinically, the nodular lesion appeared to be a benign tumor (Figure C). In each case, the nodule was excised totally and histopathologic examination revealed a well-circumscribed, nonencapsulated nodule within the mid-dermis. Thick, acellular collagen bundles were arranged randomly in short fascicles through the center of the lesion. Cellular areas consisting of histiocytes and fibroblasts with a storiform pattern at the periphery of lesion were observed, but nuclear atypia and mitotic activity were not. Results of immunohistochemical stain with CD34 were negative, but in all cases were strongly positive for Factor XIIIa. Slight epidermal hyperplasia was present with orthokeratotic hyperkeratosis and flattened rete ridges in the overlying epidermis (Figure A-1, Figure B-1, Figure C-1). The subcutaneous fat and adjacent skin were normal. No folliculosebaceous units at the periphery of the lesion were seen, but a few eccrine sweet glands were noted. No recurrence appeared in 18 months of follow-up.     

Case study: erythrokeratodermia variabilis

A 4-year-old girl presented to the dermatology clinic with complaints of erythematous skin lesions on her face, extremities,forearms, and joints. The patient was a product of a full-term, normal pregnancy and delivery and was born to healthy parents. The parents are cousins. The condition started a few months after birth with small, hyperkeratotic patches on her cheeks. These lesions did not respond to the treatment that was given. The condition progressed and a few months later similar skin lesions started to appear on her forearms and knees. Different types of treatment, such as topical antibiotics,emollients, topical steroids, and systemic antihistamines, have been tried without any benefit. Some lesions showed variable exacerbations and remissions. There was no family history of a similar problem, although her older brother showed marginal hair loss without any skin lesions. On physical examination (Figures 1-3), hyperkeratotic erythrodermic plaques of variable thickness with sharply demarcated borders were seen on cheeks, extensor surfaces of forearms, and on the knees. The palms,soles, nails, and teeth were normal. The hair showed normal appearance, but there was no hair growth on the margins of the scalp. The laboratory investigations showed normal complete blood count and normal serum zinc and ferritin levels. Urine microscopy and examination was normal. Skin biopsy was taken and histopathology showed nonspecific features of hyperkeratosis with moderate papillomatosis and acanthosis (Figure 4). A diagnosis of erythrokeratodermia variabilis was made and the patient was started on emollients as treatment. There was not much improvement with the treatment.     

A case of Kallmann syndrome with bilateral calcifications at the basal ganglia

A twenty-year-old male with hematoemesis was transported to our department in an unconscious state. His past history was epilepsy in infancy and the evacuation of an undescended testis for cryptochidism at three years of age. His familial history included duodenal ulcers and amyotrophic lateral screlosis among his relatives on his father's side of the family. On arrival, he demonstrated a sleeping tendency regardless of his stabilized vital signs. He had experienced a delayed puberty. A head CT examination revealed bilateral calcification at both the globus pallidus, caudate nucleus and periventricular regions, and an endoscopic study showed a duodenal ulcer. An EEG depicted a 2 Hz spike and slow waves in the occipital areas. An endocrinological examination demonstrated a low value of free testosterone and follicle stimulating hormone (FSH). The FSH and luteinizing hormone (LH) both demonstrated a hypo-reaction to the LH-releasing hormone test. A head MRI revealed bilateral olfactory bulb aplasia while the venous olfactory test with thiamine propyldisulfide was negative. Accordingly, he was diagnosed to have Kallmann syndrome. A follow-up endoscopic examination exhibited an improvement in his ulcer and he was also discharged on the 13th hospital day. Kallmann syndrome should thus be included in the differential diagnosis when young individuals present with calcifications in the basal ganglia.     

Tumid lupus erythematosus: an unusual scleredema-like presentation

A 43-year-old white man presented with an 8-month history of redness and swelling on the back of the neck. He also noted a decrease in range of motion of his upper body. There was no improvement with a 4-week course of topical corticosteroids. Review of systems was negative for polydipsia, polyuria, polyphagia, and bone pain. His medical history included depression, gastroesophageal reflux disease, and microdiscectomy. His medications included sertraline and omeprazole. Physical examination revealed a 20-cm erythematous, indurated plaque on the posterior part of the upper back and neck (Figure 1). A lack of skin wrinkling was noted with lateral pressure. Biopsy revealed a periadnexal and mild interface dermatitis with an increase in connective tissue mucin as demonstrated with colloidal iron (Figures 2A and 2B). Serum protein electrophoresis, hemoglobin A1C, and antinuclear antibody titer were within normal limits. A diagnosis of tumid lupus erythematosus mimicking scleredema was made. Hydroxychloroquine therapy was started at a dose of 200 mg and, at 2 months' follow-up, the patient's symptoms and appearance were improved.     

Chronic leg ulcers in Werner's syndrome.

We report two siblings suffered from Werner's syndrome, which is a rare premature aging disorder caused by genetic mutations. They developed premature aging during adolescence with loss and graying of hair, short stature, baldness, atrophic skin, thin extremities, flat feet, 'bird' face and cataracts. Multiple chronic ulcers were noted over the feet in both patients. Healing was prolonged because of atrophic subcutaneous tissue, poor perfusion, impaired fibroblast activity and the loss of normal foot architecture. Treatment of the ulcers was challenging, as flap options were limited over the lower third of the leg and skin grafting was not easy as there was a lack of healthy granulations. However, we have successfully closed the ulcers with Integra artificial skin and ultra-thin split thickness skin grafting with the scalp as donor site. The main purpose of this paper is to alert physicians to this syndrome when treatments are being planned for patients with chronic leg ulcers.     

A rose by any other name

A 40-year-old man visited Haiti in the winter. His visit was uneventful, and he went swimming in the ocean. A week after his return he developed a small "pimple" on his right fifth finger. This condition progressed for several weeks, with new lesions developing over the extensor surface of his forearm and in the antecubital fossa. He had tender axillary adenopathy. The patient started a new job when he returned from Haiti, working 4 days per week in a greenhouse. He denied any fever, chills, or night sweats. He was in good health without any underlying chronic health problems. Physical examination revealed a small eschar over the distal phalanx of the patient's right fifth finger (Figure 1). There were 2 erythematous nodules over the extensor surface of his right forearm (Figure 2) as well as over the antecubital fossa (Figure 3). A punch biopsy was performed and results showed suppurative granulomatous dermatitis. Sporothrix schenckii was grown from the specimen.     

Tropical aquarium aquatic dermatoses: bristle worm envenomation

A 55-year-old high school science teacher with diabetes presented with severe pain and swelling of his left hand. He reported receiving a "shock" 2 days earlier while cleaning out his classroom's aquarium with a bare left hand. Thinking it was a "short" in the electrical connections to the aquarium's pump, he disconnected the electrical cord and continued to clean behind the pump mechanism. After a few more such shocks he put on a glove and retrieved 10 foot-long worms. Antibiotics were started. It took more than 2 weeks for the hand to return to its normal size. On presentation to our office, the patient's left hand was moderately swollen, with blistering and purpura seen on his distal fingers. He reported pain, itching, and numbness in the hand, which was getting worse. No systemic symptoms were reported. The patient was a non-insulin-dependent diabetic who was also taking warfarin for a carotid vascular problem. He brought to our office a bucket with coiled aquatic worms at the bottom (Figure 1). When extended, they measured about 1 foot and their morphology could be better seen (Figure 2). No spicules could be seen in the patient's hand on magnification, but taping was performed to remove any possible residual spicules. The patient was given oral antibiotics, a Medrol dose pack, oral antihistamines, and topical corticosteroids. Within 1 day of starting treatment his symptoms and hand swelling began to abate, by 1 week his hand skin peeled, and by 2 weeks the swelling and skin appearance was almost back to normal. Bacterial cultures of the hand's wounds showed no growth.     

Compartment syndrome in a young male caused by acute alcoholic rhabdomyolysis

We report a case of young male who developed compartment syndrome of his left leg caused by rhabdomyolysis following a heavy binge of alcohol. The laboratory data on his admission revealed extremely elevated serum levels of CPK (108,021 IU.l-1). The serum levels of potassium and creatinine were within normal ranges. He also had myoglobinuria. He required fasciotomy after admission. Diuretics and a large volume of fluids were given to prevent the renal failure. His postoperative course was uneventful. The direct toxic effects of alcohol and the prolonged ischemia of his lower leg induced by acute alcoholic intoxication, are thought to have played a major role in the triggering of the acute rhabdomyolysis. Acute alcoholic rhabdomyolysis should be considered in any intoxicated patient who presents muscle tenderness and weakness. The early recognition and prompt treatment are essential to prevent serious complications.     

Klinefelter's syndrome presenting with leg ulcers

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.     

Cutaneous manifestations of Strongyloides stercoralis hyperinfection in an HIV-seropositive patient

A 41-year-old human immunodeficiency virus (HIV)-positive man was hospitalized with complaints of a 4-week history of nausea and vomiting, associated with decreased oral intake, and a 4-day history of frontal headache and fever. His medical history was significant for a gunshot wound to the head 3 years prior, with a residual seizure disorder. He also had two previous hospitalizations, both for culture-negative bacterial meningitis; the first episode occurred 12 months before admission and the second episode occurred 5 months later. At that time, he was found to be positive for serum antibodies against HIV and a CD4+ T-lymphocyte count of 126/mm3. He had no known drug allergies and was not receiving any medication. On admission, the patient was febrile (104.0 degrees F) and hypotensive (blood pressure, 92/40 mm Hg). Pertinent physical examination findings included cachexia with bitemporal wasting, dry mucus membranes, adherent white patches on the oral mucosa, and negative Kernig's and Brudzinski's signs. His laboratory results revealed macrocytic anemia, a decreased serum sodium of 125 mEq/L, and a normal total leukocyte count with a CD4+ T-lymphocyte count < 50/mm3. Lumbar puncture opening pressure was elevated at 160 mm Hg, and cerebrospinal fluid analysis showed an increased white cell count of 97/microL (84% lymphocytes), a decreased glucose level of 26 mg/dL, and a decreased protein level of 42 mg/dL. The patient was started on empiric therapy that included intravenous ampicillin and cefotaxime, oral Bactrim, and clotrimazole lozenges for thrush. Cerebrospinal fluid culture was positive for Escherichia coli, sensitive to cefotaxime. Two days later, the patient developed fine, erythematous, nonblanchable macules primarily on his abdomen, with minimal involvement of his thorax and back. His skin lesions remained unchanged for the next 2 weeks. Repeat lumbar puncture was performed after 14 days of cefotaxime. The cerebrospinal fluid analysis showed an elevated white cell count of 7/microL (100% lymphocytes), a decreased glucose level of 53 mg/dL, and a decreased protein level of 33 mg/dL. The cerebrospinal fluid culture was now positive for Pseudomonas aeruginosa resistant to cefotaxime. The patient was started on imipenem. On day 34 of his admission, the patient became tachypneic with complaints of dyspnea. A chest roentgenogram revealed bilateral patchy infiltrates. He was transferred to the intensive care unit and intubated for hypoxemic respiratory failure (arterial blood gas values on 6 L of oxygen: pH, 7.46; bicarbonate, 23; and oxygen saturation, 37). That evening, the patient was also noted to have diffuse petechiae and purpura in a reticulated pattern over his abdomen (Figure 1A and 1B), most heavily concentrated in the periumbilical region, extending to the axillae and upper thighs. A 3x3-mm punch biopsy from abdominal skin demonstrated Strongyloides stercoralis larvae in the dermis (Figure 2A and 2B). His sputum specimen was teeming with adult S stercoralis worms (Figure 3) and, subsequently, numerous S stercoralis larvae were observed not only from the bronchoalveolar lavage but also from the nasogastric fluid specimen. These findings confirmed the diagnosis of disseminated strongyloidiasis. On hospital day 35, the patient was doing poorly and was started on thiabendazole (1250 mg twice daily for 28 days). Nine days later, ivermectin (4.5 mg once daily for 3 days for 2 courses) was also added. He continued to clinically deteriorate. The patient died 31 days after systemic antihelminthic treatment was initiated.     

Not so acute renal failure with crystals in the urine.

Case A 40-year-old fire fighter presented to an emergency room becauseof nausea, vomiting and muscle pains in the upper arms and thighs.He had been actively engaged in his profession until the timeof admission and denied prior medical illnesses. He denied specifictrauma or drug abuse. He was uncertain as to the colour of hisurine. Physical examination disclosed a blood pressure of 125/80mmHg. His muscles were tender to palpation but normal in appearance.The chest was clear, the heart disclosed no murmurs, the abdominalexamination was normal and     

Familial isolated hyperparathyroidism: a report of two cases

A family (a brother and a sister) of the familidal isolated hyperparathyroidism (FIH) was reported. The older brother with age of 58 year-old was pointed out hypercalcemic while examining his hypertension and proteinuria. He had high levels of serum total and ionized calcium, intact-PTH and gastrin, and hypophosphatemia. His neck CT scan revealed swelling of the two parathyroid glands in each side. He underwent resection of the tumors and the auto-implantation of the glands under diagnosis of primary hyper parathyroidism. Histopathology was diagnosed to be hyperplasia of the parathyroid glands. The younger sister with age of 52 year-old was referred to our clinic because she was suffering from recurrent urolithiasis. Biochemical examination of her blood sampling resulted in very resemble values of her brother mentioned above. Her neck CT scan showed three tumors consisting of each one at the bilateral parathyroid glands and one in the thymic region. She underwent resection of the tumors and the auto-implantation of the glands and histopathological diagnosis was hyperplasia as same as her brother's one. The postoperative courses of these cases have been uneventful for four years. FIH is a low significant disease of which ten lineages have been reported in Japanese literature although it should be differentiate with such a disease of multiple endocrine neoplasms.