Acquired Perforating Dermatosis: A Disorder Treatable with Mycophenolate Mofetil.

Acquired perforating dermatosis (APD) is an adult skin disease characterized by an umbilicated papulonodular rash with transepidermal elimination of dermal components such as collagen and/or elastin. It is frequently associated with multiple medications and diseases such as diabetes and chronic renal failure. It is a disabling disease with severe pruritus in 83.3% of cases and generalized ulcerating lesions that are associated with infections and scarring. Nearly 10% of renal patients are affected. Supportive measurements of disease activity and previous medications failed to halt its natural progression. In our study, we documented significant improvements in the severity of the disease as measured by the eczema area and severity index (EASI), in 32 patients with the renal disease through the use of mycophenolate mofetil (MMF), with EASI decreasing from 31 [interquartile range (IQR) = 4] to 3 (IQR = 4) by the 3rd month. Moreover, such changes persisted for up to 2 years despite a decrease in the dose of MMF to half after 1 year. In conclusion, our study showed that MMF is a safe and effective immunosuppressive drug for short- and intermediate-term therapy of severe APD and confirmed its autoimmune etiology.

The Beneficial Effect of Three-month Induction Therapy with High-dose Prednisone and Mycophenolate Mofetil Followed by Maintenance Therapy in Acute Non-crescentic Nephritis Associated with Immunoglobulin A Deposition Disease in Adults.

The data available on immunoglobulin A (IgA) deposition disease indicate an inherited predisposition to the disease with autoimmune triggering. Hence, we prospectively evaluated the role of a new autoimmune regimen in the treatment of severe nephrotic or nephritic flares associated with noncrescentic nephritis in adult patients. Thirty-six patients were included, and the regimen consisted of an initial 3-month induction phase of prednisone and mycophenolate mofetil (MMF), followed by a maintenance phase of MMF alone for 21 months. Complete remission (CR) (normalization of creatinine clearance [CrCl] and a decrease in protein output to <500 mg/day) was achieved in 29 of 36 patients, and a partial response (no further decline in CrCl and a decrease in proteinuria to <50%) was seen in seven patients. CrCl was maintained in patients with CR but was mildly reduced in partially responsive ones. Our study showed the short- and longterm safety and efficacy of this autoimmune regimen directed toward the autoimmune triggering factors in severe forms of noncrescentic IgA nephritis.

Long-term Rituximab Therapy in Adult Patients with Idiopathic Nephrotic Syndrome.

Patients with refractory idiopathic nephrotic syndrome (INS) are at risk of infections, renal failure, and the inherent side effects of immunosuppressive therapy. In the present study, we investigated the efficacy of yearly rituximab therapy in adult patients with this syndrome over 5-10 years. In the minimal change disease group, 14 of the 15 patients had complete remission (CR) and one had partial remission (PR). Of those who achieved CR, eight patients did not require rituximab 4 years later. The patient with PR was treated in the same way as those with focal segmental glomerulosclerosis (FSGS) group and remained stable by the end of the study. In the FSGS group, rituximab therapy resulted in the amelioration of INS in nine patients, although two were non-responders (NR) and developed end-stage renal disease (ESRD). In the membranous glomerulopathy group, 36 patients had CR but two were NR and developed ESRD. Twenty (55%) of those did not require treatment after 4 years, whereas the rest maintained CR with yearly rituximab. Nine women received rituximab after the third month of pregnancy without significant adverse effects on the fetus or subsequent conception. In conclusion, rituximab is a safe, practical, and effective long-term therapy for adult patients in these three groups of INS.

Complementary bodybuilding: A potential risk for permanent kidney disease.

We report our experience of renal disease associated with bodybuilders who had been on high-protein diet, anabolic androgenic steroids (AASs), and growth hormone (GH) for years. A total of 22 adult males who volunteered information about use of high protein diet and AAS or GH were seen over a six-year period with renal disease. Kidney biopsy revealed focal segmental glomerulosclerosis (FSGS) in eight, nephroangiosclerosis in four, chronic interstitial nephritis in three, acute interstitial nephritis in two, nephrocalcinosis with chronic interstitial nephritis in two, and single patients with membranous glomerulopathy, crescentic glomerulopathy, and sclerosing glomerulonephritis. Patients with FSGS had a longer duration of exposure, late presentation, and worse prognosis. Those with interstitial disease had shorter exposure time and earlier presentation and had improved or stabilized after discontinuation of their practice. There is a need for health education for athletes and bodybuilders to inform them about the risks of renal disease involved with the use of high-protein diet, AAS, and GH.

Biopsy of small kidneys: A safe and a useful guide to potentially treatable kidney disease.

Over the past four years, all patients with unexplained rapid progression of their renal disease were subjected to kidney biopsy, despite their small size (<9 cm), to define its etiology. Children, pregnant women, morbidly obese patients, and those with an unstable cardiovascular state, septicemia, bleeding diathesis as well as those kidney size with size <6 cm were excluded from the study. Doppler ultrasound was used to exclude renovascular/ischemic nephropathy. The procedure was performed by an interventional radiologist using a biopsy gun technique and under ultrasound guidance. The actual diagnosis was established in 29 cases while seven had advanced sclerosing glomerulonephritis. Eleven cases had evidence of vasculitis, of which two were due to polyarteritis nodosa and two were due to crescentic immunoglobulin A disease. The remaining patients had a secondary form of focal segmental glomerulosclerosis (n = 4), interstitial nephritis (n = 4), malignant nephro-angiosclerosis (n = 2), and single patient with primary hyperoxaluria, light chain cast nephropathy, amyloidosis, and thrombotic microangiopathy. All, except eight with advanced glomerulosclerosis, had improved or became stable with specific treatment. Our study shows that biopsy of small-sized kidneys, in patients with unexplained renal deterioration, is safe, and its diagnostic value can improve their morbidity and even mortality.

Membranous glomerulopathy and massive cervical lymphadenopathy due to immunoglobulin G4-disease.

A 32-year-old male presented with acute and severe nephrotic syndrome as well as massive right cervical lymphadenopathy for <2 years. Computed tomography scan of the chest, abdomen, and pelvis did not reveal any lymphadenopathy. Histopathology and immunohistochemical testing of his lymph node biopsy showed infiltrate enriched with immunoglobulin G4 (IgG4)-positive plasma cells. His kidney biopsy showed granular membranous deposits of IgG4 in the basement membrane without interstitial infiltrate. Antiphospholipid 2 receptor antibodies were absent excluding its "idiopathic" nature. Since he was allergic to rituximab, he was treated with corticosteroids for two months and a combination of tacrolimus and mycophenolate. His lymphadenopathy disappeared, and his proteinuria abated. The dose of the latter two medications was reduced to half after four months and will be maintained for a minimum of two years to prevent relapse of his disease.

Hilar and para-aortic necrotizing lymphadenopathy associated with antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis.

Lymph node involvement as a part of systemic vasculitis is rare. We report a case of women with rapidly progressive renal disease associated with recurrent epigastric pain, weight loss, and massive hilar as well as para-aortic lymphadenopathy. Ultrasound-guided biopsy of her scarred kidneys revealed antineutrophil cytoplasmic antibody-negative crescentic glomerulonephritis and that of lymph nodes showed severe necrotizing vasculitis. Biopsy of the lymph nodes and the failing kidney established the diagnosis of this rare presentation and ruled out lymphoma and tuberculosis. Administration of corticosteroids and cyclophosphamide resulted in a favorable outcome.

Primary hyperoxaluria in an adult male: A rare cause of end-stage kidney disease yet potentially fatal if misdiagnosed.

Primary hyperoxaluria is an autosomal recessive disorder due to a deficiency in the activity of the peroxisomal hepatic enzyme alanine-glyoxylate aminotransferase. It is a common cause of urolithiasis and end-stage kidney disease in children contrary to the adult phenotypic presentation which is considered a mild disorder with occasional urolithiasis. In this case report, we describe a 25-year-old man who presented with advanced and irreversible kidney failure within three months following strenuous physical training in the police academy. He had nephrocalcinosis and stones in one kidney. Diagnosis was confirmed by establishing the existence of extensive tubular and interstitial crystal deposition in his kidneys and molecular genetic testing. The case illustrates the need to establish an early diagnosis of this disorder to prevent the need for combined liver and kidney transplantation.

Primary hydatid cyst of the supraspinatus muscle: complete removal of the germinal layer and cytodiagnosis by fine-needle aspiration.

Primary hydatid disease of the skeletal muscle without systemic involvement is rare. The purpose of this report is to document the novel clinical presentation and the interesting facets of fine-needle aspiration in a case of hydatid disease. It was a case of primary hydatid cyst of the left supraspinatus muscle in an Indian woman living in Kuwait, which was clinically diagnosed as a lipoma. Fine-needle aspiration (FNA) yielded 2 ml of clear fluid with white particulate material. The cytocentrifuged smears prepared from the aspirated fluid showed many scolices, occasional laminated cyst wall fragments and numerous hooklets. The laminated cyst wall and scolices were PAS positive. Trichrome staining imparted a demon-head-like appearance to the scolices. The cytodiagnosis of hydatid cyst was corroborated by histopathological examination of an excised whitish membrane and an irregular cystic fragment, which showed parallel laminations without germinal layer, and skeletal muscle with granulomas and a dense eosinophilic infiltration, respectively. Quantitative serological (indirect hemagglutination) test on blood sample collected 9 days after the excision of the cyst showed insignificant antibody titer to Echinococcus sp. and after 6 weeks the antibodies were completely absent. CT scan of the chest and abdomen performed 7 weeks after removal of cyst showed no evidence of visceral hydatid cyst.

Splenectomy complicated by sustained extreme thrombocytosis and extensive portosplenomesenteric vein thrombosis in pyrimidine 5'-nucleotidase deficiency.

Reactive and redistributional thrombocytosis is a well-known postsplenectomy occurrence .Usually it is transient and it rarely reaches extreme levels. We report a rare case of haemolytic anaemia where splenectomy was carried out following trauma to a massively enlarged spleen and was followed by extreme sustained thrombocytosis associated with extensive portal, splenic and mesenteric vein thrombosis despite standard antithrombotic prophylaxis.

Rituximab therapy for severe cutaneous leukocytoclastic angiitis refractory to corticosteroids, cellcept and cyclophosphamide.

We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to <0.1 one week following the start of retuximab had increased to >0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

Radiologic features of granulomatous mastitis.

Granulomatous mastitis (GM) is a recognized, but an uncommon cause of breast mass. Awareness of this condition is important, because it can clinically as well as radiologically mimic breast carcinoma. In this study, we present the imaging features of a series of 10 cases with proved diagnosis of granulomatous mastitis with emphasis on magnetic resonance (MR) findings. All those patients who were histologically proven to have GM of the breast were analyzed. Their files were reviewed and data recorded for demographic, clinical presentation and imaging appearances. The imaging features of the lesions by mammography, ultrasound, and magnetic resonance imaging were analyzed. Of the 305 patients who were surgically treated, 10 (3%) cases proved to have GM. All the patients were females with age ranging from 27 to 53 years (average 38 years and median age 36 years). Guided core biopsy was performed in all cases for confirmation of diagnosis followed by either excision biopsy (in five cases) or lumpectomy (in five cases). The final histopathologic results were chronic granulomatous inflammation consistent with tuberculosis in four cases and GM with acute inflammation, but unknown etiology in four cases and GM due to duct ectasia in two cases. GM, a rare breast condition, should be considered in the differential diagnosis of patients with a breast mass associated with inflammatory change. Routine breast imaging with US, MG, or MRI, the condition from malignant lesions and biopsy, still remains the only method of definite diagnosis.

Papillary thyroid carcinoma: how much should the surgeon read from fine needle aspiration cytology reports?

OBJECTIVE: During routine fine needle aspiration cytodiagnosis of papillary thyroid carcinoma (PTC), a number of cases are diagnosed as suspicious; or it is suggested that PTC or a neoplasm be ruled out by histopathology. Since these diagnostic labels are likely to put the clinicians in a difficult situation while planning the management, this study aims to find out how much the surgeon should read from these reports. MATERIALS AND METHODS: The patients were divided into two groups. Group A included 38 cases diagnosed as PTC or suspicious of PTC. Group B included 40 cases in which it was suggested that PTC/a neoplasm to be ruled out and non-neoplastic lesions with one or more cytologic features of PTC. The two groups were compared with clinical, imaging and cytomorphologic features. RESULTS: A significant difference was observed with respect to age between Group A and Group B (P<0.001). The frequency of the following five cytologic features was significantly higher in Group A: papillary formation (P<0.001), psammoma bodies (P=0.054), fine nuclear chromatin (P=0.010), frequent nuclear grooves (P<0.001) and intra-nuclear cytoplasmic inclusion (P<0.001). Three or more of the five cytologic features were also reported in significantly higher number of Group A cases (P<0.001). Majority (81.8%) of the cases with subsequent histology in Group A were confirmed as PTC as opposed to 7.7% in Group B (P<0.001). CONCLUSIONS: Thus, cases with definitive cytodiagnosis of PTC and suggestive of PTC (Group A) should be taken much more seriously by the surgeons as compared to Group B cases.

Accuracy of the Fischer scoring system and the Breast Imaging Reporting and Data System in identification of malignant breast lesions.

BACKGROUND AND OBJECTIVES: Fischer developed a scoring system in 1999 that made identifying malignnant lesions much easier for inexperienced radiologists. Our study was performed to assess whether this scoring system would help beginners to accurately diagnose breast lesions on magnetic resonance (MR) imaging and to assess the correlation between the magnetic resonance mammography Breast Imaging Reporting and Data System (MRM BI-RADS) grade and the final diagnosis. PATIENTS AND METHODS: The lesion morphology and contrast kinetics of 63 masses in 41 patients were evaluated on MRI and accorded a MRM BI-RADS final assessment category using the Fischer scoring system. The accuracy was evaluated after the final diagnosis was obtained by tissue sampling and follow-up imaging. RESULTS: There were 25 malignant and 30 benign lesions. Eight lesions were seen by MRI only and we could not verify their pathology since we did not have MR-guided biopsy facilities at the time of the study. On MR mammography, the proven carcinomatous lesions were characterized as BI-RADS category V in 16 (64%), category IV in 7 (28%), and category III in 2 (8%) lesions. Benign lesions were graded as category V in 3 (10%), category IV in 6 (20%), and category III in 3 (10%), category II in 10 (33%) and category I in 8 (27%) lesions. The MRM BI-RADS category accurately predicted malignancy in 92% and a benign pathology in 70% of the lesions. The overlap between the MRM features of chronic inflammatory lesions and carcinomas resulted in a lower accuracy in diagnosing benign as compared to malignant lesions. CONCLUSION: The MRM BI-RADS lexicon using the Fischer scoring system is useful and has a high predictive value, especially for malignant breast lesions, and is easy to apply. Overlapping features between benign inflammatory and malignant lesions might yield a reduced accuracy in inflammatory pathologies.

Hodgkin's lymphoma: diagnostic difficulties in fine-needle aspiration cytology.

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non-Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed-Sternberg (R-S)-like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine-needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty-one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin-like cells and typical R-S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnosis of HL.

Breast magnetic resonance imaging: initial experience in Kuwait.

OBJECTIVE: To report our initial experience of breast magnetic resonance imaging (MRI) in Kuwait in order to identify and characterize breast lesions. SUBJECTS AND METHODS: In 58 patients ranging in age from 25 to 64 years, breast MRI was performed as a problem-solving tool (29); for suspicious local relapse of the treated breast (6); to search for a primary breast cancer in patients with metastatic axillary lymph nodes (5); for local staging of breast cancer (5); breast implants (6); screening in high-risk patients (3), and differentiation between inflammation and inflammatory carcinoma (4). Sagittal fat-saturated T(2) and axial T(1) images were obtained before, and axial fat-saturated T(1) and dynamic sagittal fat-saturated T(1)-weighted images after contrast enhancement in a 1.5-tesla closed magnet. The diagnostic criteria were based on the morphology and kinetics of the lesion. Findings were validated by tissue sampling or radiological follow-up. RESULTS: Seventy breast lesions (25 malignant, 38 benign and 7 lesions detected by MRI only) were identified in the 58 patients. The sensitivity, specificity, and positive and negative predictive values of MRI in diagnosing malignant breast lesions were 96, 67, 71 and 95%, respectively, while the accuracy was 80%. CONCLUSION: This initial experience is comparable to other published data. Future plans for improving image spatial resolution and MR-guided procedures have been taken into consideration.

Accuracy of the Fischer scoring system and the Breast Imaging Reporting and Data System in identification of malignant breast lesions.

BACKGROUND AND OBJECTIVES: Fischer developed a scoring system in 1999 that made identifying malignant lesions much easier for inexperienced radiologists. Our study was performed to assess whether this scoring system would help beginners to accurately diagnose breast lesions on magnetic resonance (MR) imaging and to assess the correlation between the magnetic resonance mammography Breast Imaging Reporting and Data System (MRM BI-RADS) grade and the final diagnosis. PATIENTS AND METHODS: The lesion morphology and contrast kinetics of 63 masses in 41 patients were evaluated on MRI and accorded a MRM BI-RADS final assessment category using the Fischer scoring system. The accuracy was evaluated after the final diagnosis was obtained by tissue sampling and follow-up imaging. RESULTS: There were 25 malignant and 30 benign lesions. Eight lesions were seen by MRI only and we could not verify their pathology since we did not have MR-guided biopsy facilities at the time of the study. On MR mammography, the proven carcinomatous lesions were characterized as BI-RADS category V in 16 (64%), category IV in 7 (28%), and category III in 2 (8%) lesions. Benign lesions were graded as category V in 3 (10%), category IV in 6 (20%), and category III in 3 (10%), category II in 10 (33%) and category I in 8 (27%) lesions. The MRM BI-RADS category accurately predicted malignancy in 92% and a benign pathology in 70% of the lesions. The overlap between the MRM features of chronic inflammatory lesions and carcinomas resulted in a lower accuracy in diagnosing benign as compared to malignant lesions. CONCLUSION: The MRM BI-RADS lexicon using the Fischer scoring system is useful and has a high predictive value, especially for malignant breast lesions, and is easy to apply. Overlapping features between benign inflammatory and malignant lesions might yield a reduced accuracy in inflammatory pathologies.

Combination of immunosuppressive agents in treatment of steroid-resistant minimal change disease and primary focal segmental glomerulosclerosis.

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. METHODS: Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. RESULTS: With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. CONCLUSION: Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.

Postmortem biopsies: the experience in Kuwait.

OBJECTIVE: To report our 4-year experience in postmortem needle biopsy of liver, heart, kidney and lung tissues when formal autopsy could not be performed. SUBJECTS AND METHODS: In the period from January 2000 to December 2003, postmortem biopsies were done at Al-Amiri Hospital, Kuwait, in 19 cases where the original diagnosis or cause of death was not clear. The procedure was performed by a dedicated trained medical team using a biopsy needle or limited incisions guided by the knowledge of the clinical presentation and results of laboratory and radiological investigations. RESULTS: The actual diagnosis was established in 8 cases by postmortem histological findings and corrected in another 9 cases. In the remaining 2 cases with systemic sepsis, autopsy only confirmed the antemortem clinical diagnosis. CONCLUSION: Our study shows that needle biopsy is an adequate technique for postmortem examination and should be considered as the minimum alternative to conventional autopsy.