Anu Anna George

Cerebrovascular injury in cryptococcal meningitis

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

Rare Presentation of Disseminated Histoplasmosis in an Immunocompetent Host

A 40-year-old gentleman from West Bengal, who is a farmer by profession, presented with easy fatigability, significant loss of weight, and asymptomatic, progressive nodulo-ulcerative lesions on his groins of 1 year duration. He gave no history of exploring caves or exposure to any large areas contaminated with bird droppings. General examination revealed firm, non-tender, discrete cervical, axillary, and inguinal lymphadenopathy. Systemic examination was within normal limits. Cutaneous examination showed dull erythematous, non-tender, and firm papules and nodules, few with central ulceration on both groins (Figures 1 and ​and22 ). There were no other skin lesions seen. The differentials considered were cutaneous tuberculosis, gummatous syphilis, atypical mycobacterial infection, nocardiosis, blastomycosis, sporotrichosis, and histiocytosis. A skin biopsy showed dense lymphoplasmahistiocytic infiltrates in the dermis with multinucleate giant cells containing budding yeasts (Figures 3 and ​and44 ). Fungal culture on Sabouraud Dextrose Agar medium showed growth of floccose, velvety, buff colored colonies on the obverse with brown pigmentation on the reverse, which were confirmed to be Histoplasma capsulatum (Figures 5​5–7). Blood investigations to look for immunosuppression including human immunodeficiency virus antibodies were negative. A computerized tomography (CT) scan of the abdomen showed large hypodense lesions in both adrenals. His chest X-ray and bone marrow examination were within normal limits. A diagnosis of disseminated histoplasmosis was made based on the skin biopsy showing intracellular yeasts, which on culture grew colonies of H. capsulatum, and the CT scan showing involvement of both adrenals. Figure 1. Ulcerated plaque in the groin of a patient with disseminated histoplasmosis. Figure 2. Erythematous, nodular lesions in the groin of a patient with disseminated histoplasmosis. Figure 3. Periodic acid–Schiff (PAS) histopathology. Photomicrograph showing PAS-positive yeasts in the deep dermis. Figure 4. Gomori methanamine silver stain histopathology. Photomicrograph showing Gomori methanamine silver-positive yeasts in the deep dermis. Figure 5. Sabouraud Dextrose Agar medium showing floccose, velvety, and buff colored colonies of Histoplasma capsulatum on the obverse. Figure 6. Sabouraud Dextrose Agar medium showing brown color on the reverse. Figure 7. Lactophenol cotton blue preparation from the culture plate showing septate, hyaline hyphae with large thick-walled spherical macroconidia with the external walls showing finger-like projections. Histoplasmosis is a highly infectious mycosis caused by an intracellular fungus H. capsulatum. Histoplasmosis is endemic in the Ohio and Mississippi River Valleys of the United States, central and South America, and Africa, but is less frequently reported in Asia and Europe.1 As pointed by Antinori,2 in India, this disease is predominantly seen along the Gangetic belt of northeast India. It can present as acute pulmonary, chronic pulmonary, acute progressive, chronic disseminated, and primary cutaneous forms. The risk factors for the acquisition of the disease include acquired immunodeficiency syndrome, primary and acquired immunodeficiency states, post transplant patients, and patients on immunosuppressive medications and extremes of age.3 In immunocompetent individuals, the disease usually manifests as an asymptomatic pulmonary infection. Disseminated histoplasmosis with cutaneous lesions is very rare in immunocompetent hosts.1 Oral ulcers are the most common mucocutaneous presentation in immunocompetent individuals with disseminated histoplasmosis.4 Cutaneous lesions of disseminated histoplasmosis are most commonly seen on the face, arms, and legs. The rarer sites of involvement, which have been reported include hands, feet, chest, back, penis, and perianal region.5 The oral lesions of histoplasmosis described in literature range from nodules, vegetating plaques to shallow or deep ulcers. The various cutaneous manifestations mentioned in literature include papules (including molluscum contagiosum–like lesions, acneiform eruptions), plaques, pustules, and nodules.5 This case is being reported to highlight the presentation of disseminated histoplasmosis at a rare site in an immunocompetent individual.

Yellow nail syndrome in rheumatoid arthritis: an aetiology beyond thiol drugs

Yellow nail syndrome (YNS) is a rare entity characterized by a triad of nail changes, lymphoedema and lung involvement. We report a 57-year-old man with rheumatoid arthritis (RA) and YNS. We have reviewed the previous case reports of RA and YNS and discuss the pulmonary manifestations.

Systemic T cell lymphoma presenting as cutis verticis gyrata

Sir, A 34-year-old man, presented with progressive swelling and serous discharge on his face and scalp for 4 months. General examination revealed pallor and multiple, enlarged, non-tender, discrete, mobile lymph nodes in bilateral cervical, axillary, and inguinal regions, the largest of which was 5 cm × 6 cm in the right axillary region, associated with hepatosplenomegaly. He had a leonine facies. The skin of the scalp was thrown into cerebriform folds with diffuse loss of hair [Figure 1a]. There was generalized xerosis with a few scattered infiltrated nodules [Figure 1b] on the trunk and extremities ranging in size from 1-2 cm and diffuse scaling over the palms and soles. The differentials considered were lymphedema secondary to a lymphatic obstruction, leukemoid/lymphomatous infiltration and sarcoidosis. On hematological examination, he was found to have anemia (10.8 g/ dl) and leukocytosis (63.4 × 109/L) associated with a serum lactate dehydrogenase of 1110 U/L. Serology for Epstein-Barr virus and human T-lymphotrophic virus were negative. Skin biopsies done from the scalp and a nodule on the back showed mild lamellar hyperkeratosis, focal parakeratosis and irregular acanthosis of the epidermis. There was a pan-dermal, moderate to dense infiltrate of medium sized lymphoid cells with vesicular nuclei, irregular nuclear membranes, small nucleoli and scant cytoplasm. Numerous apoptotic bodies were seen [Figure 2a and b]. On immunohistochemistry, these cells were positive for CD3 [Figure 3a], CD4 [Figure 3b], focally positive for CD25 [Figure 3c] and negative for CD5, CD7, CD20, CD34 and terminal deoxynucleotidyl transferase. The MIB-1 proliferation index [Figure 3d] was 85%. Lymph node biopsy from the right axilla was consistent with high grade T-cell lymphoma on histopathology and immunohistochemistry [Figure 4]. Bone marrow biopsy showed myeloid hyperplasia with increased eosinophils and its precursors. T cell receptor re-arrangement studies demonstrated clonality for the alpha-beta type. CD 3 and CD 4 positivity indicated a T cell lymphoma. CD 20 negativity ruled out a B cell lymphoma. CD 7, CD 34 and terminal deoxynucleotidyl transferase negativity ruled out a T cell lymphoblastic leukemia/lymphoma. CD 25 positivity is usually seen in adult T cell lymphoma, which was ruled out in view of the human T lymphotropic virus serology being negative. A high MIB-1 proliferation index indicated a high grade lymphoma. On this basis the diagnosis of high grade T cell non-Hodgkin lymphoma was

Rifampicin-induced immune allergic reaction

1. Whiley RA and Duke B. Heterogeneity among 6S-23S rRNA intergenic spacers of species within the Streptococcus milleri group. Microbiology 1995; 141: 1461–1467. 2. Facklam R. What happened to the Streptococci: overview of the taxonomic and nomenclature changes? Clin Microbiol Rev 2002; 15: 613–630. 3. Bert F, Bariou-Lancelin M and Lambert –Zechovsky N. Clinical significance of bacteremia involving the ‘‘Streptococcus milleri’’ group: 51 cases and review. Clin Infect Dis 1998; 27: 385–387. 4. Enterococci S. Streptococcus-like bacteria. In. Winn W, Jr., Allen S, Janda W, et al. (eds) Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. 6th edn. Philadelphia, PA: J.B. Lippincott Company, 2006, pp.674–745. 5. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility; twenty-fifth informational supplement. CLSI document M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute, 2015; 35: 3. 6. Laupland KB, Ross T, Church DL, et al. Populationbased surveillance of invasive pyogenic streptococcal infection in a large Canadian region. Clin Microbiol Infect 2006; 12: 224–230. 7. Igra-Siegman Y, Azmon Y and Schwartz D. Milleri group Streptococcia stepchild in the viridians family. Eur J Clin Microbiol Infect Dis 2012; 31: 2453–2459. 8. Dorvilus P and Edoo-Sowah R. Streptococcus milleri: a cause of pyogenic liver abscess. J Natl Med Assoc 2001; 93: 276–277. 9. Clarridge JE III, Attorri SM and Musher DM. Streptococcus intermedius, Streptococcus constellatus and Streptococcus anginosus (Streptococcus milleri group) are of different clinical importance and not equally associated with abscess. Clin Infect Dis 2001; 32: 1511–1515. 10. Limia A, Jimenez ML, Alarcon T, et al. Five year analysis of antimicrobial susceptibility of the Streptococci milleri group. Eur J Clin Microbiol Infect Dis 1999; 18: 440–444.

Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients

BACKGROUND Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. METHODS We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. RESULTS Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. CONCLUSIONS These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

Recurrent pericardial effusion and tamponade in a patient with Erdheim-Chester disease (ECD)

Erdheim-Chester disease (ECD) is a rare xanthogranulomatous disorder characterised by the proliferation of lipid laden histiocytes along with infiltration of various organs of the body. Although commonly presenting with bone pains secondary to bony infiltration, cardiac involvement in the form of periaortic fibrosis and pericardial involvement may be seen in a subgroup of patients. We report a case of ECD presenting as recurrent pericardial effusion along with pericardial tamponade.

Annular cutaneous sarcoidosis with systemic involvement

Sarcoidosis is a granulomatous disease involving multiple systems. Cutaneous involvement is present in 25% of patients. A 42-year-old woman presented with itchy skin lesions on her face for 5 years duration. She was found to have annular and discoid plaques with prominent overlying telangiectasia. A biopsy from the plaque was suggestive of sarcoidosis. On further evaluation, she was found to have both pulmonary and ocular involvements. Annular sarcoidosis is a rare variant of cutaneous sarcoidosis. We report this case to highlight this rare variant of sarcoidosis and discuss the various cutaneous manifestations of sarcoidosis.

Etiological and clinicopathological study of secondary small vessel vasculitis in elderly: A case series of 12 patients

Background: Inflammation involving the postcapillary venular wall is defined as small vessel vasculitis. Small vessel vasculitis has various clinical manifestations. Etiologically, it can be primary or secondary. Literature regarding secondary vasculitis in elderly is scanty. Aim and Objectives: In this case series, we aimed to assess the clinical features and etiologies of biopsy-proven secondary small vessel vasculitis in the elderly. Methodology: Twelve elderly patients with biopsy-proven small vessel vasculitis were included in this study. All patients were thoroughly evaluated to assess the etiology and presence of major organ involvement. Results: Secondary small vessel vasculitis involved both the sexes equally. Constitutional symptoms including fever and weight loss were noticed by most of the (70%) patients. Neurological deficits were present in 83% of the study population. The most common finding in an electromyographic examination was an asymmetric sensory motor distal predominant polyradiculopathy. Fifty percent of the patients did fulfill the criteria for a definite autoimmune disease. More than 30% of the vasculitis was secondary to malignancies. Conclusions: Neurological manifestations are the most common systemic involvement in elderly patients with secondary vasculitis. Meticulous search for underlying malignancies is mandatory in elderly patients with secondary small vessel vasculitis.

Renal cell carcinoma presenting as a cutaneous horn and nodules on the gingiva and scalp

A 63-year-old man presented with a pulsatile cutaneous horn on the nose and multiple angiomatous nodules on the gingiva and scalp, which appeared over 2 months. He had severe hypercalcaemia, lytic lesions in multiple bones and acute kidney injury. Excision biopsy from the gingival nodule showed a clear cell neoplasm. The bone marrow showed atypical cells with similar morphology. Imaging showed a 7 cmx7.5 cm mass at the upper pole of the left kidney with metastases to the bones, liver and lung. Immunohistochemistry was consistent with metastatic renal cell carcinoma. Renal cell carcinoma presenting as a cutaneous horn is extremely rare and to the best of our knowledge only one other case was found in the literature. There was visible regression in the size of the cutaneous horn and nodules following initiation of pazopanib therapy. However, he succumbed to his illness a month later.