Mild Lymphocytic Infiltration Research Articles

Clonal characteristics of paired infiltrating and circulating B lymphocyte repertoire in patients with primary biliary cholangitis.

PBC is a prototypical autoimmune liver disease characterized by portal lymphoplasmacyte infiltration. ALD is a prototypical environment-driven disease, featured by mild lymphocyte infiltration. We hypothesize that B cells are more involved in the pathogenesis of PBC. By analysing the infiltrating B cell repertoire, we aimed to unveil greater oligoclonal expansion and active clonal exchange between liver and periphery in PBC than in ALD patients. Using NGS of Ig H chain genes, we analysed the liver-infiltrating and paired peripheral B lymphocyte repertoire from nine PBC and four ALD patients. In the liver of PBC and ALD patients, (i) roughly 10% of the B lymphocytes were clonally related and highly expressed, and there were also lineages that underwent extensive clonal expansion; (ii) there was different use of IGHV/IGHJ segments between PBC and ALD, suggesting distinct Ag exposure backgrounds, but this did not lead to a significant difference in their clonal expansion level. Analysis of data sets from paired samples further revealed, (iii) direct clonal exchange and evolutionally related B cell clones between the infiltrating and peripheral repertoire; (iv) the seeding of the infiltrating clones to periphery, and peripheral ones to the liver, for further extensive evolution. The oligoclonally expanded nature of the infiltrating B cell repertoire implies B cell immunity is involved in the pathogenesis of both diseases. The observed clonal exchange might provide an approach to identify and monitor the infiltrating B cells through the periphery.

Primary Hyperoxaluria: A Case Report and Review of the Literature

: Oxalate nephropathy is a rare cause of renal failure. Primary Hyperoxaluria (PH) is due to glyoxylate metabolism disorders with specific hepatic enzyme deficiencies. Secondary hyperoxaluria is caused by increased intestinal absorption, excessive dietary intake or excessive intake of oxalate precursors. This study reports on a 4-month-old male with high serum creatinine level, low serum sodium and calcium, high uric acid, and low urine specific gravity. Sonography showed calcification of medullary papilla (nephrocalcinosis). In kidney biopsy, many polarizing intra-tubular and interstitial calcium oxalate crystals, mild patchy lymphocytic infiltration, and interstitial fibrosis were noted. Despite supportive therapies and correction of fluid and electrolyte abnormalities, the patient gradually became oliguric progressing to anuria, and was placed on peritoneal dialysis.

A study on histopathological changes in lesions of vitiligo in Karnataka population

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Vitiligo is considered to be symptom less and its presentation is boundless varying from isolated focal lesion to bizarre generalized lesions. The present study was undertaken to study the histopathological changes in lesions of vitiligo in south Indian population.</span></p><p class="abstract"><strong>Methods:</strong> 150 patients with mild to moderate vitiligo features attending the outpatient department of Dermatology, Venereology and Leprology at Chitageri General Hospital and Bapuji Hospital attached to J.J.M Medical College, Davengere were utilized to study the histopathological features in vitiligo and its association with other diseases.<strong></strong></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">Destruction of melanocytes at dermo-epidermal junction was noted. We have observed presence of melanocytes in the basal layer of the epidermis on left side of the lesion, whereas decreased melanocytes in the basal layer of the epidermis on the right side of the same lesion in the present study. Dermis with mild perivascular lymphocytic infiltration and acanthosis along with mono nuclear cell infiltration in the upper dermis was observed. </span></p><p class="abstract"><strong>Conclusions:</strong> <span lang="EN-IN">The present study gives better knowledge to the clinicians about the lesions of vitiligo and its pathogenesis.</span></p>

Morgellons Disease

Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination showed only mild lymphocytic infiltration, and failed to reveal evidence of any microorganism. The polymerase chain reaction for Borrelia burgdorferi was negative in her serum.

Colonic epithelial nodular hyperplasia associated with strongyloidiasis in cats in the Amazon region, Pará State, Brazil

ABSTRACT: Strongyloides spp. are intestinal parasites that affect several animal species. Four species of the genus have been reported in domestic cats: S. felis, S. planiceps, S.stercoralis and S. tumefaciens . Reports describing infection by these nematodes in domestic cats in Brazil are scarce. This study aimed to describe the pathological features of Strongyloides spp. parasitism in two cats in the Amazon region, state of Pará, Brazil. During the necropsy of the two cats, numerous whitish nodules approximately 0.2cm in diameter were observed in the wall of the large intestine. The nodules were conspicuous in the colonic mucosa and exhibited a punctate aperture facing the center of the lumen. Microscopically, these nodules were formed by projections of the mucosal epithelium into the submucosa, which formed tubules lined with a single layer of columnar epithelium, with high cellularity and rare goblet cells, characterizing epithelial hyperplasia of the crypts. Adult nematodes and eggs observed in the lumen of the tubules were morphologically compatible with Strongyloides spp. Numerous larvae were also observed in the interstitium adjacent to the nodule. A mild lymphocytic infiltrate was observed neighboring the hyperplastic nodules. The histological changes are consistent with those described for S. tumefaciens infection.

Hypophysitis Secondary to Cytotoxic T-Lymphocyte–Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series

Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathologic examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathologic evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathologic evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms.

Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.

SummaryInduced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment.

Pathologic Features of Colorectal Inflammatory Polyps in Miniature Dachshunds.

The histopathologic characteristics of colorectal inflammatory polyps that formed in Miniature Dachshunds were compared with those of other colorectal proliferative lesions, including adenomas and adenocarcinomas. Fifty-three colorectal polypoid lesions were histopathologically classified into inflammatory polyps (26 cases), adenoma (18 cases), and adenocarcinoma (9 cases). All 26 dogs that were diagnosed with inflammatory polyps were Miniature Dachshunds, indicating that colorectal inflammatory polyps exhibit a marked predilection for this breed. The inflammatory polyps had complex histopathologic features and were classified into 3 stages based on their epithelial composition. In early stage (stage 1), the polyps tended to exhibit a thickened mucosa containing hyperplastic goblet cells, dilated crypts filled with a large amount of mucus, and mild lymphocyte and macrophage infiltration. In later stages (stages 2 and 3), more severe neutrophil infiltration, interstitial mucus accumulation, granulation tissue, and occasional osteoid tissue were seen. Also, a few small foci of dysplastic epithelial cells were detected. The hyperplastic goblet cells, which were a major component of the epithelium of the inflammatory polyps, were positive for cytokeratin 20 (CK20), while the dysplastic epithelial cells found in inflammatory polyps (stage 3) and the tumor cells of the adenomas and adenocarcinomas were negative for CK20. These CK20-negative epithelial cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin. In addition, the epithelial cells in the inflammatory polyps demonstrated significantly higher cyclooxygenase 2 and fibroblast growth factor 2 expression than did those of the adenomas and adenocarcinomas, suggesting that the arachidonate cascade is involved in the development of colorectal inflammatory polyps in miniature dachshunds.

Coexistence of Classic and a Mononuclear Variant of Juvenile Xanthogranuloma in an Adult Patient.

Dear Editor: Juvenile xanthogranuloma (JXG) is histologically characterized by dense mononuclear cells with foamy histiocytes and Touton giant cells in a background of lymphocytes and eosinophils1,2,3. An unusual variant of non-lipidized JXG has been described in approximately 28 cases, in which Touton giant cells and foam cells are absent or very scant. These cases are described as non-lipidized JXG, early JXG, or a mononuclear JXG variant1,3,4,5. This variant is typically found in infants or children younger than three years and presents most commonly as a solitary lesion1,4. There have been few reports of mononuclear JXG variants occurring in adults3,4. We report an adult female presenting with multiple lesions, consisting of both classic JXG and a mononuclear JXG variant. A 20-year-old Korean female presented with a red-to-yellow, dome-shaped asymptomatic scalp nodule that had developed within the last 4 months (Fig. 1A). Subsequently, two additional lesions appeared on her back and thigh, presenting as two yellow papules (Fig. 2B, C). The back lesion was excised, and histologic analysis revealed a dense infiltrate of epithelioid mononuclear cells, with a few containing cytoplasmic vacuoles. However, neither Touton giant cells nor well-developed, foamy histiocytes were detected (Fig. 2A, B). Based on the clinical and histological findings, a mononuclear JXG variant was suspected. Fig. 1 (A) A 20-year-old female presented with a 4-month history of a red-to-yellow dome-shaped, asymptomatic, ulcerated nodule on the scalp. (B and C) Subsequently, two small yellow lesions developed on the patient's back and thigh, with similar appearances ... Fig. 2 (A) Proliferation of monomorphous epithelioid cells with mild lymphocytic infiltrates in the excised lesion from the back (H&E, ×40). (B) Higher magnification demonstrates dense epithelioid to spindle-shaped mononuclear cells without foamy ... Two weeks after the excision, a punch biopsy of the scalp lesion was performed. The specimen showed mixed proliferation of histiocytes, lymphocytes, and giant cells. Cells were frequently accompanied by a well-developed foamy cytoplasm, and multinucleated giant cells were easily detected, most of which were of the Touton type (Fig. 2C~E). Based on typical clinical and histological JXG features, the second biopsy specimen of the back lesion, for which the histological features were ambiguous, was diagnosed as a mononuclear JXG variant. The thigh lesion, which was clinically similar, was diagnosed as the same entity. As the initially excised back lesion developed after the scalp lesion, the lack of typical JXG features could be due to insufficient development. This theory is supported by the histologic changes present during JXG development1,5. Kubota et al.5 suggested that the JXG developmental course, inflammatory cell components, and persistent duration of a few years support the idea that JXG may be a reactive disease. In summary, several atypical findings that confounded the diagnosis were observed in the current case. First, most cases of mononuclear JXG variants involving multiple lesions have been reported in younger children, with a male preference2. However, our patient was an adult female with multifocal cutaneous lesions. Second, multiple lesions appeared within a short period (4 months), resulting in coexistence of a fully developed lesion and immature lesions in early evolutionary stages. The simultaneous presence of these uncommon features in a single patient is unique, and this supports the hypothesis that JXG may develop through a reactive rather than neoplastic process5.

IP3R deficit underlies loss of salivary fluid secretion in Sjögren's Syndrome.

The autoimmune exocrinopathy, Sjögren’s syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca2+ release, critically required for Ca2+ entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca2+]i elevation were detected in acinar cells from lymphotoxin-alpha (LTα) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT α, a cytokine linked to disease progression in SS and IL14α mice, reduced Ca2+ signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients.

Coexistence of porokeratosis ptychotropica with porokeratosis of Mibelli in a Chinese man.

Coexistence of porokeratosis ptychotropica with porokeratosis of Mibelli in a Chinese man.

Prurigo Pigmentosa

Prurigo pigmentosa (PP) is a rare inflammatory dermatosis originally reported in Japan. Since then, most reports have originated from Asia, and to a lesser extent from Europe. Although the pathogenesis remains unclear, it is now established that PP is linked to ketoacidotic states. Four patients diagnosed with PP were identified from the dermatopathology database at the American University of Beirut Medical Center between January 2009 and December 2013. Clinicopathologic findings in the 4 patients were similar to those previously reported in the literature. The patients were all female with a mean age of 23.5 years. They all presented with itchy erythematous reticulated papulovesicles/plaques leaving variable reticulated brownish patches. Two patients had, in addition, annular lesions arranged en cocarde and pustules, respectively. In 3 patients, the rash was associated with fasting or dieting. The rash had a predilection to the trunk and proximal part of the upper extremities. One patient had intergluteal area involvement. Two biopsy specimens revealed psoriasiform hyperplasia and neutrophilic exocytosis mimicking psoriasis or an impetiginized spongiotic dermatitis. One biopsy specimen exhibited a mild superficial perivascular lymphocytic infiltrate with ballooning and reticular degeneration, a picture mimicking a viral exanthema. Another biopsy specimen exhibited a picture similar to chronic spongiotic dermatitis. Although mostly described in Japan, PP has been described much less frequently in the Middle East region likely due to mis/underdiagnosis. Therefore, increased awareness is necessary especially because fasting is a common religious practice among Arab countries. Further investigations are necessary to better understand the etiopathogenesis of this rare entity.

Gamma Knife rhizotomy-induced histopathology in multiple sclerosis-related trigeminal neuralgia.

In this report, the authors describe the pathological changes in the human trigeminal nerve after Gamma Knife radiosurgery. Three trigeminal nerves of patients with multiple sclerosis (MS)-related trigeminal neuralgia (MSTN) after Gamma Knife radiosurgery and other ablative procedures were examined by a neuropathologist. These cases were compared with 3 patients with typical TN who underwent partial surgical rhizotomy following recurrent symptoms after gasserian injury procedures, as well as with autopsy specimens from patients with and without MSTN. The three irradiated MS-TN specimens exhibited axon loss, demyelination, myelin debris, and fibrosis. Mild lymphocytic infiltrate was present in all 3 samples from MS-TN patients. The nonirradiated trigeminal nerve samples were generally well myelinated with rare degenerating axons. The microscopic findings in trigeminal nerve autopsy specimens were normal in patients without TN, with MS but not TN, and MS-TN. The inflammation observed in MS-TN specimens collected following Gamma Knife radiosurgery has not previously been described in the literature. These data provide new insight into the changes that occur in trigeminal nerve following stereotactic radiosurgery.

VCA at Innsbruck Medical University - An Update 14 Years After the First Hand Transplantation.

Background We describe here the outcome after two bilateral hand, one bilateral forearm and one unilateral hand transplantation at 14, 11, 8 and 5 years after transplantation. Patients Since March 2000, four patients received a bilateral hand, a bilateral forearm or a unilateral hand transplantation at Innsbruck Medical University. All patients received induction therapy. Antithymocyte globulin or alemtuzumab was followed by tacrolimus, prednisolon, MMF or tacrolimus and MMF maintenance immunosuppression (IS). Later, sirolimus/everolimus was added under simultaneous withdrawal or dose reduction of tacrolimus or MMF. Steroids were avoided in one and withdrawn in two patients. Results Hand function correlated well with time after transplant and amputation level. Intrinsic hand muscle function recovery and discriminative sensation were observed in all patients. Complications included CMV infection, fungal infection, hypertension, hyperglycemia, transient creatinine increase and headache and a bullous pemphigoid. Three, six, four, and two rejection episodes, thereof two DSA+ antibody-mediated rejections, were successfully treated with steroids, anti-CD25, anti-CD52 and anti-CD20 antibodies and/or intensified maintenance IS. Skin histology at current shows no or mild perivascular lymphocytic infiltrates without signs of progression. Radiomorphological studies do not show any signs for luminal narrowing of vessels. Conclusion The overall functional outcome and patient satisfaction after bilateral hand, bilateral forearm and unilateral hand transplantation are highly encouraging. All patients are now free of rejection with moderate levels of IS.

A novel morphologic-molecular recurrence predictive model refines traditional prognostic tools for invasive breast carcinoma.

Histologic grade, TNM stage, and Nottingham Prognostic Index are traditional prognostic tools for breast cancer. "IHC-molecular" classification of breast cancer can also identify patients at different recurrence risks and provides insight into cancer therapy. However, cancers in each group are heterogeneous. A model based on the comprehensive analysis of morphologic features and molecular subtype was constructed to predict recurrence and refine these traditional prognostic tools. Morphologic features including histologic grade, fibrotic focus, extensive intraductal component, lymphocytic infiltrate, lymphovascular invasion, tumor necrosis, tumor margin and TNM stage, and molecular subtypes approximated by immunohistochemistry were analyzed in 633 patients with invasive breast carcinoma (excluding those with HER2 targeted therapy). Significant independent predictors for recurrence included: high histologic grade (p = 0.004), presence of lymphovascular invasion (p = 0.004), fibrotic focus (p = 0.020), mild lymphocytic infiltrate (p = 0.013), high TNM stage (p < 0.001), and HER2-overexpressing (p = 0.004) and basal-like (p < 0.001) molecular subtypes. A morphologic-molecular recurrence predictive model based on these features was useful in recurrence prediction, independent of treatment modalities, and was able to refine the traditional prognostic tools of histologic grade, TNM stage, and Nottingham prognostic index, particularly for intermediate-risk groups, and to refine the luminal group molecular subtypes. Such findings were reproducible with a validation cohort. TNM stage, histologic grade, lymphovascular invasion, fibrotic focus, mild lymphocytic infiltrate, HER2-overexpressing and basal-like molecular subtypes were important independent recurrence risk factors for breast cancer. This morphologic-molecular model was robust in recurrence prediction and refined recurrence risk stratified by the traditional prognostic parameters, independent of treatment modalities.

An Incidental Subepithelial Mass in the Esophagus

Question: A 79-year-old man was referred to our hospital because of an incidental subepithelial lesion (SEL) in the esophagus. A mass, approximately 1.0 cm in size, covered with normal esophageal mucosa was detected in the mid-esophagus (Figure A). Endoscopic ultrasonography using a 20-MHz mini-probe revealed a homogeneously hypoechoic lesion with lobulated margins in the deep mucosal and submucosal layers (Figure B). Endoscopic biopsy revealed marginally increased proliferation of squamous epithelium with mild lymphocytic infiltration. Follow-up endoscopy was recommended because of the patient’s advanced age and the benign mesenchymal tumor indicated by endoscopic ultrasonography. Follow-up endoscopy was performed 6 months later, showing that the SEL had increased in size and the surface was more lobulated (Figure C). Endoscopic submucosal dissection was performed for definitive diagnosis and treatment. What is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The tumor was resected en bloc by endoscopic submucosal dissection, without complications. On histopathologic examination, the mass was covered with normal squamous epithelium (Figure D) and tumor cell nests were seen surrounded by dense lymphoid infiltration beneath the intact squamous epithelium (Figure E). These findings are consistent with lymphoepithelioma-like carcinoma (LELC); the invasion depth was deep submucosal invasion (sm3) and mild lymphatic invasion was observed. The results of in situ hybridization for Epstein-Barr virus were negative. The patients received additional concurrent chemoradiation because of prior coronary artery bypass grafting. No recurrence or distant metastases were detected 10 months after endoscopic submucosal dissection. Esophageal LELCs are extremely rare, with only 17 cases being previously reported in the English literature. Endoscopically, most esophageal LELCs appear as SELs and may be confused with benign tumors such as leiomyoma.1Nakasono M. Hirokawa M. Suzuki M. et al.Lymphoepithelioma-like carcinoma of the esophagus: report of a case with non-progressive behavior.J Gastroenterol Hepatol. 2007; 22: 2344-2347Crossref PubMed Scopus (10) Google Scholar Although most LELCs in the stomach are related to Epstein–Barr virus infection, in situ hybridization for Epstein-Barr virus is negative in more than half of the reported cases of esophageal LELC.2Chen P.C. Pan C.C. Hsu W.H. et al.Epstein-Barr virus-associated lymphoepithelioma-like carcinoma of the esophagus.Hum Pathol. 2003; 34: 407-411Crossref PubMed Scopus (31) Google Scholar In conclusion, physicians should be aware that LELC mimics benign SELs on endoscopy and should be included in the differential diagnosis of a SEL in the esophagus.

Non-Eczematous Vesiculobullous Skin Eruption after Stevens-Johnson Syndrome: Developed without Intravenous Immunoglobulin Therapy.

Dear Editor: Pompholyx is a chronic relapsing inflammatory vesiculobullous skin disease of the hands and feet that is histologically characterized by intraepidermal spongiotic vesicle formation with epidermal and dermal inflammatory cell infiltration1. Intravenous immunoglobulin (IVIG) administration has been proposed to be a cause of pompholyx in previous reports2,3,4. There is one case report for non-eczematous vesiculobullous eruption induced by IVIG in a patient with Stevens-Johnson syndrome (SJS)5. We report a case of non-eczematous vesiculobullous skin eruption occurred in the recovery period of SJS treated only with systemic steroid. This study is approved by Catholic Medical Center (IRB No. SC13RISI0040). A 30-year-old man presented to the emergency center with asymptomatic multiple erythematous papules and plaques on the whole body and painful erosion of the lips and conjunctivae. He had taken allopurinol for 3 weeks for hyperuricemia. He was referred to the dermatology department for the skin manifestations and was admitted under the diagnosis of SJS. He had fever up to 40.2℃ which went up and down for 12 days without any evidence of infection. Systemic steroid was administered for 2 weeks. On the next day of the last steroid adminstration, the patient presented newly developed vesiculobullous lesions on both palms (Fig. 1). They were asymptomatic multiple clear vesicles and the biopsy specimen showed an intracorneal vesicle with hyperkeratosis and acanthosis. Mild lymphocytic infiltration without eosinophil in the papillary dermis was observed (Fig. 2A, B). He had no history of pompholyx. The vesicles resolved spontaneously in 2 weeks. Fig. 1 Asymptomatic multiple clear vesicles on the palms. Fig. 2 (A, B) The biopsy specimen showed an intracorneal vesicle with hyperkeratosis and acanthosis with mild lymphocytic infiltration in the papillary dermis (HE A: ×40, B: ×200). There are many reports about IVIG-induced pompholyx in patients with various neurologic diseases or SJS which were considered as an adverse effect of IVIG, one of the uncommon cutaneous reactions including urticaria, erythema multiforme, and morbiliform eruption. Although the mechanism of IVIG-induced vesiculobullous eruption has not been elucidated, higher dose and fast flow rate of IVIG might affect its development3,4. Lin et al.5 reported a case of non-eczematous vesiculobullous eruption following SJS treated with IVIG. In previous reports, eczematous and non-eczematous vesicles resolved spontaneously, or with topical or systemic steroids in 3 or more weeks3,4,5. In this case, we started systemic steroid therapy for rapid clinical recovery, instead of IVIG. The vesicles on the palms appeared just after the steroid cessation and subsided spontaneously within 2 weeks. While histopathology of pompholyx demonstrates intraepidermal spongiotic vesicle with eosinophils and lymphocytes, the biopsy specimen of this case showed an intracorneal vesicle and only mild lymphocyte infiltration which is not consistent with pompholyx. We assumed that the perspiration related to the fever and scales from the skin regeneration process aggregated to plug the sweat pores and create such lesions. It is a new opinion that the vesiculobullous eruption could be provoked by SJS itself at the end of the disease course, rather than by the adverse effect of IVIG. This case implies the possibility that the pathophysiological mechanism differs from the one that explains the development of transient pompholyx induced by IVIG, since the steroid, the major therapeutic drug of eczema, had been administered regularly until the day just before the vesicles appeared.

Evaluation of Lead Hepatotoxicity; Histological, Histochemical and Ultrastructural Study

Lead is one of the most well-known naturally occurring environmental heavy metals. This experimental study was designed to evaluate lead induced toxic effects on hepatocytes and lobular architecture as judged microscopically. Material and Methods: This study was conducted in anatomy department, Benha faculty of medicine, Benha University, Egypt from May to October 2013 on 30 normal adult albino rats divided into 3 groups; one control and 2 experimental groups. The experimental groups were given 0.13% lead acetate solution in drinking water for 4 and 8 weeks, respectively. Animals were scarified and livers were removed and used to identify microscopic changes. Specimens were stained with Hematoxylin and eosin, with Masson trichrome stain for study of fibrous tissue and with periodic acid shiff's (PAS) to study the glycogen content. Other specimens were prepared for ultrastructural study. Results: Mild lymphocytic infiltration, vacuolar degeneration and mild increase of periportal fibrosis with mild depletion of glycogen content and partial disappearance of glycogen vacuoles were reported in animals received contaminated water for 4 weeks. Animals maintained for 8 weeks on contaminated water showed hepatic changes in the form of abundant lymphocytic infiltration, increased cellular polymorphism, pyknotic nuclei and areas of cell necrosis with evident moderate periportal fibrosis and marked vacuolar degeneration associated with marked depletion of glycogen content. Ultrastructural study revealed mitochondrial edema, appearance of interstitial inflammatory cells, and appearance of scattered variable sized lead electron-dense inclusion bodies. Conclusion: It could be concluded that chronic exposure to lead imposes a potent toxic effect on liver cells manifested as glycogen depletion, cellular infiltration and liver architecture in the form of initiation of periportal fibrosis that may progress to liver cirrhosis.

Updated diagnosis criteria for confluent and reticulated papillomatosis: a case report.

Dear Editor: Confluent and reticulated papillomatosis (CRP), a rare skin disorder of unknown etiology, is characterized by hyperkeratotic papules confluent in the central area and reticulated hyperpigmented patch in the peripheral area1. Since Gougerot and Carteud first identified CRP in 1927, this disease has been diagnosed by using clinical courses, histological findings, and treatment results. However, other diseases, such as fungal infection or other pigmentary skin diseases, were frequently misdiagnosed as CRP because of the lack of diagnostic criteria for CRP. Therefore, Davis et al.1 proposed the diagnostic criteria for CRP on the basis of a study on 39 patients, as follows: (i) clinical findings of scaly brown macules and patches, with at least some appearing reticulated and papillomatous; (ii) involvement of the upper trunk and neck; (iii) negative fungal staining of scales; (iv) no response to antifungal treatment; and (v) excellent response to minocycline. However, a few cases of CRP sparing the upper trunk have also shown the typical histopathological findings, clinical findings, and treatment responses of CRP. A 42-year-old Korean woman presented to our clinic with a 4-year history of asymptomatic, brownish, and reticulated skin lesions in her antecubital and axillary regions (Fig. 1A). She reported that her skin lesions had worsened in May and improved slightly in October without any specific treatment. We performed a potassium hydroxide test to rule out fungal infection. Because the test result was negative at the antecubital fossa but positive at the axilla, we began treatment with oral itraconazole and topical flutrimazole cream for 2 weeks. Despite the 2 weeks of treatment, her skin lesions persisted. We then performed an axillary skin biopsy. Histopathological evaluation revealed papillomatosis and hyperkeratosis of the epidermis, and downward growth of the epidermis between the rete ridges (Fig. 2). Periodic acid Schiff staining did not reveal any fungal organism. On the basis of these findings, we diagnosed her condition as CRP limited to the flexural areas. After 2 months of doxycycline treatment (100 mg twice a day), her skin lesions completely disappeared (Fig. 1B). Fig. 1 (A) Hyperpigmented scaly macules with a reticular pattern on the axilla and antecubital fossa. (B) Complete resolution of the skin lesions after 2 months of doxycycline treatment. Fig. 2 Histopathological findings of the axillary lesion showing an orthokeratotic epidermis with acanthosis and papillomatosis plus mild perivascular lymphocytic infiltrate in the superficial dermis (H&E, ×200). Our patient exhibited only limited lesions at the antecubital fossae and axilla, which is inconsistent with the previous diagnostic criteria for CRP1. Several cases of CRP had involved various flexural areas alone, including the axilla2,3, popliteal fossa2, or antecubital regions4. These lesions fulfilled other diagnostic criteria for CRP. Therefore the criteria related to the primary affected sites should be revised. In addition, the criteria for fungal staining and response to antifungal treatment should be modified. Occasionally, CRP and fungal infection coexist5, as in this patient, however an important diagnostic consideration is that CRP lesions cannot be improved with antifungal treatment even in the presence of a positive fungal examination. Finally, minocycline3,4 has been known as the treatment of choice for CRP; however, other antibiotics have also been efficacious3. The exact reason for the effect of antibiotics is unclear, but many dermatologists speculate that their anti-inflammatory effect may be more predominant than their anti-bacterial effect1. As mentioned above, the previous diagnostic criteria for CRP had several limitations in cases of unusually involved location, co-infection with fungus, and use of antibiotics other than minocycline. Therefore, we propose a modified diagnostic criteria, as follows: (i) clinical findings includeing scaly brown macules and patches, with at least some appearing reticulated and papillomatous; (ii) involvement of the upper trunk, neck, or flexural areas; (iii) negative fungal staining of scales or no response to antifungal treatment; and (iv) excellent response to antibiotics.

AugmentinTM-induced DILI: A Case of Severe Cholestatic Jaundice with Spontaneous Resolution

Introduction: Drug-induced liver injury (DILI) is a major cause of iatrogenic illness, and may present with an array of histologic signatures. Establishing a diagnosis of DILI requires a careful exclusion of other etiologies and an awareness of the hepatotoxicity profile of suspected agents. Case: A 70-year-old man with a history of HTN, CAD, AF, and BPH was referred for a six-day history of intense pruritus, associated with jaundice, dark urine, and acholic stool. He denied any abdominal pain, weight loss, recent travel, fevers/chills, or sick contacts. Physical exam revealed a jaundiced patient with no cutaneous stigmata of chronic liver disease, and no hepatosplenomegaly, ascites, or asterixis. On presentation, his LFT's were as follows: T bili 7.5, D bili 4.6, AST 34, ALT 45, ALP 232, GGTP 63, alb 3.8, and normal INR. Serologies revealed a negative HAV IgM, HBSAg, HB core IgM, HCV PCR, ANA, SMA, AMA, anti-LKM, P-ANCA, ACE, and normal immunoglobulins. Doppler U/S revealed a normal liver morphology with a small hepatic cyst, patent hepatic vessels, normal gallbladder, no biliary ductal dilation and no hepatosplenomegaly or ascites. MRCP revealed a normal biliary tree with no pruning. Within 10 days of presentation, his T bili peaked at 20.9 with an ALP of 274. On further inquiry, the patient recalled a two-week course of amoxicillin/clavulanate (AugmentinTM) for a URI, with his symptoms beginning one week after discontinuation of the antibiotics. A liver biopsy revealed mild cholestasis, spotty necrosis/apoptosis, lymphocyte, neutrophil, and eosinophil infiltration consistent with a drug-induced hepatitis. There was no bile duct damage, ductopenia, granulomas, or fibrosis. The patient was prescribed cholestyramine four g BID for pruritus, and urso 250 mg BID. Within eight weeks, his LFT's had completely normalized. Discussion: Amoxicillin/clavulanate- induced DILI is estimated to occur with an incidence of 17/100,000 prescriptions, and the clavulanic acid component is the likely injurious agent. This idiosyncratic reaction is thought to be immunoallergic in origin, and autoantibody formation is uncommon. Men over 50 years of age and prolonged/repeated courses of AugmentinTM are associated with an increased risk of DILI. Although cases of acute liver failure and chronic ductopenia have been described with AugmentinTM, a delayed cholestatic or a mixed cholestatic-hepatocellular liver injury pattern is the norm, and usually resolves within two months. Despite our patient being an elderly male who developed marked jaundice, his course was ultimately benign, with full resolution of symptoms.