Hypokalaemic hypertension and 17-alpha-hydroxylase/17,20-lyase deficiency in a young girl: a case report

Hong Kong Med J 2024 Jun;30(3):241–4 | Epub 31 May 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Hypokalaemic hypertension and 17-alpha-hydroxylase/17,20-lyase deficiency in a young girl: a case report
HN Yau, FHKCPaed, FHKAM (Paediatrics)1; WC Lo, FHKCPaed, FHKAM (Paediatrics)2; YP Yuen, FHKAM (Pathology), FRCPA3; MT Leung, FHKCPath, FHKAM (Pathology)4; KL Ng, FHKAM (Paediatrics), FRCPCH2
1 Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Hong Kong SAR, China
2 Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Hong Kong SAR, China
3 Department of Pathology, Hong Kong Children’s Hospital, Hong Kong SAR, China
4 Department of Pathology, Queen Elizabeth Hospital, Hong Kong SAR, China
 
Corresponding author: Dr HN Yau (nicoleyau@fellow.hkam.hk)
 
 Full paper in PDF
 
 
Case presentation
A young girl aged 9 years 6 months was admitted to hospital in July 2022 with coronavirus disease 2019 infection and found to have refractory hypokalaemia. She reported good past health and denied taking any supplements or medications. Her nonconsanguineous parents and 4-year-old younger brother were healthy and family history was unremarkable.
 
Her body weight and height were 35.8 kg at the 75th to 95th percentile and 140 cm at the 75th percentile, respectively. Her body mass index was 18.3 kg/m2 at the 75th percentile. Blood pressure was noted to be persistently high up to 152/117 mm Hg (112/73 mm Hg being the 90th percentile for her gender, age and height according to the American Academy of Pediatrics1). Cardiovascular and abdominal examinations were unremarkable. There was no hyperpigmentation or sign of virilisation. She was prepubertal, with normal female external genitalia.
 
Ambulatory blood pressure monitoring confirmed stage 2 hypertension. Electrolytes and hormone profile are summarised in the Table. Her bone age was 8 years 10 months according to the Greulich and Pyle method of assessment. A standard-dose Synacthen test did not stimulate a rise in 17-hydroxyprogesterone or cortisol level. Ultrasound of the pelvis revealed prepubertal uterus and bilateral ovaries. Her karyotype was 46,XX.
 

Table. Investigation results before and after treatment
 
Urine steroid profile showed a characteristic pattern compatible with 17-alpha-hydroxylase/17,20-lyase deficiency (17OHD), with a lack of androgen metabolites and an excess of progesterone, pregnenolone, and corticosterone metabolites (online supplementary Appendix).
 
Oral hydrocortisone was commenced at 7.6 mg/m2/day. Blood pressure improved to 119/81 mm Hg after 2 weeks. Spironolactone was added for better control.
 
Genetic analysis revealed compound heterozygous pathogenic variants in the CYP17A1 gene: c.297+2T>C in intron 1 and c.849delC p.(Ser284Glnfs*13) in exon 5, which confirmed the diagnosis of 17OHD. Parental testing confirmed that the two CYP17A1 variants were in trans, and the younger brother was a carrier.
 
Discussion
17-alpha-hydroxylase/17,20-lyase deficiency is a rare type of congenital adrenal hyperplasia that accounts for 1% of cases with an estimated incidence of 1 in 50 000 to 100 000.2 17-alpha-hydroxylase and 17,20-lyase enzyme defects result in cortisol and sex hormone deficiency, with compensatory rise in adrenocorticotropic hormone that drives excessive production of 11-deoxycorticosterone and corticosterone (Fig).3
 

Figure. Pathophysiology in steroidogenesis pathway in 17-alpha-hydroxylase/17,20-lyase deficiency
 
Unlike the pathophysiology of the more common types of congenital adrenal hyperplasia such as 21-hydroxylase deficiency and 11-beta-hydroxylase deficiency, 17OHD does not cause excessive testosterone production with consequent virilisation in affected 46,XX females or precocious puberty in both sexes.3 Instead, due to the lack of sex steroid hormone production, it results in undervirilisation in 46,XY males and sexual infantilism in 46,XX females.3 The excessive accumulation of deoxycorticosterone and corticosterone exerts potent mineralocorticoid effects, resulting in sodium and fluid retention, hence suppression of renin with hypokalaemic hypertension,2 as in our patient. A high concentration of corticosterone provides sufficient glucocorticoid effect to prevent adrenal crisis.3 The classic presentation of 17OHD is a phenotypic female with delayed puberty, primary amenorrhoea, and hypokalaemic hypertension with diagnosis often made in young adulthood.2 4 5 Cases of retained partial enzyme activity resulting in ambiguous genitalia in 46,XY males have been reported.3 4
 
Delayed diagnosis of 17OHD is not uncommon due to its subtle and late presentation. Hypokalaemic hypertension should prompt a clinician to search for secondary causes of hypertension. Plasma renin activity is an important investigation to differentiate the causes, and would be suppressed in 17OHD by the potent mineralocorticoid activity, and is high in renovascular disease.6 On the contrary, aldosterone level could be suppressed, normal or raised in 17OHD.2 4 5 Low aldosterone level arises as a result of a suppressed renin angiotensin system while high level might be related to more severe enzyme defects resulting in greater production of end product from aldosterone precursors.4 As 17OHD has a characteristic pattern of metabolite excretion and metabolite ratios on urine steroid profiling, this profiling is an important investigation when diagnosing the condition.
 
There is no consensus guideline on the management of 17OHD. The mainstay of treatment is glucocorticoid and sex hormone replacement. The use of glucocorticoid would decrease the adrenocorticotropic hormone drive and production of deoxycorticosterone and corticosterone, which would facilitate improved blood pressure control and electrolyte balance.2 Different forms and dosages of glucocorticoid replacement have been described in the literature, ranging from dexamethasone 0.25 mg to 1 mg daily, or equivalent.2 4 5 In some cases, an antihypertensive agent with a mineralocorticoid antagonist effect such as spironolactone or eplerenone may be required for blood pressure control.3 5 Patients may develop end organ damage such as hypertensive retinopathy if blood pressure control is suboptimal.2 Deoxycorticosterone and corticosterone levels might not be normalised despite treatment. Blood pressure control, electrolyte balance, and renin level are more important markers of disease control.4
 
Our patient was phenotypically female, in line with her genotypic sex. Her hormone blood test revealed hypergonadotropic hypogonadism due to lack of sex hormone production. Oestrogen and progestin replacement should be commenced at an appropriate time during adolescence, or upon diagnosis in adulthood, to induce secondary sexual characteristics and cyclic uterine bleeding.5 Sex steroid replacement therapy may improve bone mineral density in 17OHD patients and prevent osteoporosis. For genotypic males, psychological assessment should determine gender preference prior to initiation of sex hormone replacement, and intraabdominal testes should be removed to prevent malignant change.3 A multidisciplinary team approach involving an endocrinologist, surgeon, psychiatrist, psychologist and social worker is essential and can help in parental counselling, achieving family consensus for gender assignment, and formulation of an individualised plan for each patient.
 
Genetic test on CYP17A1 is important to make the diagnosis of 17OHD. To date, the Human Gene Mutation Database has reported >100 different types of mutations on the CYP17A1 gene.7 Genetic analysis showed compound heterozygous pathogenic variants in the CYP17A1 gene (reference transcript: NM_000102.4): c.297+2T>C in intron 1 and c.849delC p.(Ser284Glnfs*13) in exon 5. c.297+2T>C is a splice site variant that has been previously described in patients with 17OHD (ClinVar accession No.: VCV0004319808), while c.849delC is a truncating variant that creates a premature termination codon. It is expected to result in an absent or disrupted protein product (ClinVar accession No.: VCV0014174348). This variant has an extremely low minor allele frequency in the general population and has not been reported in patients with CYP17A1-related disease.
 
17-alpha-hydroxylase/17,20-lyase deficiency is associated with infertility due to premature follicular arrest and poor endometrial development for implantation.9 Women with 17OHD have difficulty conceiving, even with the help of assisted reproductive technology.9 Though not promising, fertility had been possible for patients with partial 17OHD. Patients should be counselled about potential fertility difficulties and referred to an assisted reproductive service when appropriate.
 
To conclude, 17OHD should be considered in a young hypertensive individual with hypokalaemia. Timely management with glucocorticoid and sex hormone replacement can ameliorate the morbidity of hypertension and hypogonadism. Multidisciplinary collaboration is advised, especially for patients with gender identification or infertility issues.
 
Author contributions
All authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. The parents of the patient provided written consent for publication of this case report.
 
Supplementary material
The supplementary material was provided by the authors and some information may not have been peer reviewed. Accepted supplementary material will be published as submitted by the authors, without any editing or formatting. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by the Hong Kong Academy of Medicine or the Hong Kong Medical Association. The Hong Kong Academy of Medicine and the Hong Kong Medical Association disclaim all liability and responsibility arising from any reliance placed on the content.
 
References
1. Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017;140:e20171904. Crossref
2. Kim SM, Rhee JH. A case of 17 alpha-hydroxylase deficiency. Clin Exp Reprod Med 2015;42:72-6. Crossref
3. Auchus RJ. Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol 2017;165(Pt A):71-8. Crossref
4. Peter M, Sippell WG, Wernze H. Diagnosis and treatment of 17-hydroxylase deficiency. J Steroid Biochem Mol Biol 1993;45:107-16. Crossref
5. Han LH, Wang L, Wu XY. 17 alpha-hydroxylase deficiency: a case report of young Chinese woman with a rare gene mutation. Clin Case Rep 2022;10:e6109. Crossref
6. Choi KB. Hypertensive hypokalemic disorders. Electrolytes Blood Press 2007;5:34-41. Crossref
7. Institute of Medical Genetics in Cardiff. Human Gene Mutation Database. Available from: https://www.hgmd.cf.ac.uk/ac/index.php. Accessed 24 May 2024.
8. National Center for Biotechnology Information, National Library of Medicine. ClinVar. Available from: https://www.ncbi.nlm.nih.gov/clinvar/". Accessed 24 May 2024.
9. Marsh CA, Auchus RJ. Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency. Fertil Steril 2014;101:317-22.Crossref

Multisystem inflammatory syndrome in adults in Hong Kong: two case reports

Hong Kong Med J 2024 Apr;30(2):173–5 | Epub 16 Apr 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Multisystem inflammatory syndrome in adults in Hong Kong: two case reports
Abram JY Chan, MB, BS, FHKAM (Medicine)1; Judianna SY Yu, MB, BS, FHKAM (Medicine)2; Alwin WT Yeung, MB, BS, FRCP2; HP Shum, MB, BS, MD3; KC Lung, MB, BS, FRCP1
1 Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China
2 Department of Medicine and Geriatrics, Ruttonjee and Tang Shiu Kin Hospitals, Hong Kong SAR, China
3 Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China
 
Corresponding author: Dr Abram JY Chan (cjy548@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentations
Case 1
A 51-year-old Chinese woman presented to Pamela Youde Nethersole Eastern Hospital on 29 September 2022 with a 1-week history of intermittent fever and confusion. She enjoyed good past health and had received three doses of Comirnaty vaccine with the last dose administered on 18 February 2022. She was first symptomatic and with a positive rapid antigen test for coronavirus disease 2019 (COVID-19) on 2 September 2022. She recovered after 8 days without the need for antiviral therapy. Respiratory samples over the initial 4 days of admission were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR). Magnetic resonance imaging of the brain on 30 September 2022 revealed focal cytotoxic oedema in the splenium of the corpus callosum, possibly indicative of encephalitis or encephalopathy (Fig a). Chest X-ray on admission revealed diffuse right lung opacities (Fig b). The chest symptoms of the patient deteriorated with bilateral involvement and increased need for oxygen support, and she was transferred to the intensive care unit with use of a high-flow nasal cannula. She was intubated on 2 October 2022 as oxygenation was suboptimal. Lumbar puncture was unremarkable. Chest X-ray on 5 October 2022 showed dense bilateral opacities (Fig c), and computed tomography of the thorax on 5 October 2022 showed bilateral pulmonary consolidations and diffuse ground glass opacities. She also developed anaemia (haemoglobin level: 7.9 g/dL) and thrombocytopenia (platelet count: 78 × 109/L). She was in a hyperinflammatory state with ferritin level of 14057 pmol/L, C-reactive protein level of 273 mg/L, lactate dehydrogenase level of 1081 IU/L, and persistently elevated D-dimer level of >8000 ng/mL. Immunoglobulin G antibody level against SARS-CoV-2 receptor-binding domain on 3 October 2022 was 34 225.34 AU/mL. The patient was otherwise haemodynamically stable. Electrocardiogram showed sinus rhythm and high-sensitivity troponin I level was only mildly elevated (19.7-119 ng/L).
 

Figure. Case 1. (a) T2-weighted hyperintense signal in the splenium of the corpus callosum (arrow) suggestive of cytotoxic oedema and may represent encephalitis or encephalopathy. Chest X-ray on admission (b), upon starting immunosuppressive therapy (c), on completion of immunosuppressive therapy (d), and on discharge (e)
 
BioFire FilmArray Pneumonia Panel for endotracheal aspirate detected 105 copies/mL of Staphylococcus aureus while mecA/C gene was not detected, and culture also grew scanty methicillin-sensitive S aureus. Cytomegalovirus DNA PCR was negative. Repeated respiratory samples including nasopharyngeal/throat swabs, sputum and endotracheal aspirate did not detect SARS-CoV-2 RNA. Pneumocystis jirovecii pneumonia PCR was negative as was sputum for acid-fast bacillus smear/c/st. Autoimmune workup including antinuclear antibody, antineutrophil autoantibodies and immunoglobulin pattern was negative. The patient was initially prescribed empirical meningitis treatment with intravenous ceftriaxone 2 g Q12H and intravenous acyclovir 500 mg Q8H, and antimicrobials were switched to piperacillin-tazobactam on 2 October 2022 after cerebrospinal fluid results excluded meningitis. Her condition continued to deteriorate while on antibiotics.
 
The patient was suspected of having multisystem inflammatory syndrome in adults (MIS-A) and was started on intravenous methylprednisolone and intravenous immunoglobulin (IVIG) from 5 October 2022. She was initially given a daily dose of methylprednisolone 0.5 g for 3 days and IVIG 20 g for 5 days. She gradually improved with decreased oxygen requirement and ventilatory support and was extubated on 7 October 2022. There was significant improvement in inflammatory markers with C-reactive protein level decreased to 30.8 mg/L, ferritin level decreased to 4746 pmol/L, and lactate dehydrogenase level decreased to 526 IU/L at the end of treatment. Serial chest X-ray showed radiological improvement with decreased bilateral opacities (Fig d) and near-resolution of chest X-ray upon discharge (Fig e) 16 days after starting MIS-A treatment. She completed a 9-week course of steroids with full recovery. A repeated magnetic resonance imaging of the brain was scheduled 7 months after discharge to monitor her progress, which showed resolution of previously noted oedema in the splenium of the corpus callosum.
 
Case 2
A 39-year-old Malawian man presented to Ruttonjee and Tang Shiu Kin Hospitals on 1 November 2022 with a history of fever since 29 October 2022. He had had confirmed COVID-19 infection with nasopharyngeal swab SARS-CoV-2 PCR positive on 7 October 2022 but recovered without the need of antivirals. He had a history of malaria 21 years ago but no travel history over the last 2 years. He otherwise enjoyed good past health apart from obesity (body weight: 120 kg; body mass index: >30 kg/m2). He had received two doses of CoronaVac and one dose of Comirnaty vaccines with the last dose administered on 2 March 2022. His fever persisted and he was noted to have bilateral conjunctivitis and petechiae over the throat. Electrocardiogram later revealed new atrial fibrillation and serial echocardiograms showed accumulation of pericardial effusion and worsening left ventricular ejection fraction of 30%. He had acute liver failure with elevated parenchymal enzyme level (alanine transaminase level: 1079 IU/L), coagulopathy (international normalised ratio: 2.61), hyperammonaemia (serum ammonia level: 108 μmol/L), and hyperlactatemia (lactate concentration: 6.65 mmol/L). He also developed acute kidney injury (creatinine level: 256 μmol/L, estimated glomerular filtration rate: 26 mL/min/1.73 m2) and thrombocytopenia (platelet count: 35×109/L). He was transferred to the intensive care unit for further management on 6 November 2022. He was in a hyperinflammatory state with ferritin level of 131 351 pmol/L, C-reactive protein level of 442 mg/mL, lactate dehydrogenase level of 7710 IU/L, and persistently elevated D-dimer level of >8000 ng/mL. Immunoglobulin G antibody level against SARS-CoV-2 receptor-binding domain on 6 November 2022 was >40 000 AU/mL. He was haemodynamically stable throughout his admission.
 
The patient was suspected of having MIS-A and was commenced on intravenous methylprednisolone (0.5 g for 6 days) and IVIG (20 g for 5 days) on 8 November 2022. His fever subsided soon after steroids were given, with resolution of organ failure. He was discharged 11 days after starting MIS-A treatment with prednisolone 40 mg twice daily. Repeated echocardiogram on 16 November 2022 prior to discharge showed significant improvement with left ventricular ejection fraction of 55% and decreased pericardial effusion of up to 1.1 cm in thickness. He had no further episodes of atrial fibrillation. He was last seen 4 weeks post-discharge and remained well on a tapering dose of prednisolone. He remained well and was eventually weaned off immunosuppressants in early October 2023.
 
Discussion
The Centers for Disease Control and Prevention case definition for MIS-A was developed through expert opinion and states that the patient should be aged ≥21 years, have been hospitalised for at least 1 day or died as a result, and fulfilled certain clinical and laboratory criteria with no more likely alternative diagnosis.1 Case 1 did not fulfil these primary clinical criteria for MIS-A. Nonetheless she exhibited the neurological and haematological components of the secondary clinical criteria and also met the laboratory criteria with no other cause identified. Fulminant pulmonary involvement is unusual since pulmonary involvement has been used to distinguish MIS-A patients from patients with severe COVID-19 infection.2 Chronologically the patient developed fulminant pneumonitis 3 weeks after her initial COVID-19 infection, within the commonly described 2- to 5-week interval between onset of typical COVID-19 symptoms and onset of MIS-A, that likely represented a post-acute phenomenon rather than part of the initial infection. A case series in the United States also reported that MIS-A patients may have pulmonary involvement and require mechanical ventilation when compared with multisystem inflammatory syndrome in paediatric patients.3 Although 86% to 89% of MIS-A patients have one or more cardiovascular abnormalities,4 the lack of cardiac involvement in this patient with otherwise compatible clinical features should not have excluded the diagnosis of MIS-A.
 
Case 2 fulfilled the Centers for Disease Control and Prevention case definition as well as having markedly deranged liver and renal function. Despite his impaired left ventricular ejection fraction, there was no shock or congestion to explain the deranged liver and renal function. Both liver and renal function recovered with immunosuppression, suggesting reversibility with treatment of the hyperinflammatory state. Such hepatic involvement has been reported in a case in Croatia5 and renal involvement has been reported previously, albeit usually associated with shock.2
 
Both cases responded rapidly to methylprednisolone and IVIG. This treatment regimen was with reference to the guidelines published by the National Institutes of Health and extrapolated from multisystem inflammatory syndrome in children data.6 Case 2 had a longer course of methylprednisolone based on body weight and higher level of inflammatory markers. Steroid tapering was initiated afterwards and continued for at least 2 months in both our patients. Further studies would be helpful to guide the management for MIS-A.
 
Author contributions
All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patients were treated in accordance with the Declaration of Helsinki. Verbal consent for treatments, procedures and for publication has been obtained from the patients.
 
References
1. Centers for Disease Control and Prevention, United States Department of Health and Human Services. CDC case definition for MIS-A. Updated January 2023. Available from: https://www.cdc.gov/mis/mis-a/hcp.html. Accessed 15 Jan 2023.
2. Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection—United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep 2020;69:1450-6.Crossref
3. Patel P, DeCuir J, Abrams J, Campbell AP, Godfred-Cato S, Belay ED. Clinical characteristics of multisystem inflammatory syndrome in adults: a systematic review. JAMA Netw Open 2021;4:e2126456. Crossref
4. Lai CC, Hsu CK, Hsueh SC, Yen MY, Ko WC, Hsueh PR. Multisystem inflammatory syndrome in adults: characteristics, treatment, and outcomes. J Med Virol 2023;95:e28426. Crossref
5. Vujaklija Brajković A, Zlopaša O, Gubarev Vrdoljak N, Goran T, Lovrić D, Radonić R. Acute liver and cardiac failure in multisystem inflammatory syndrome in adults after COVID-19. Clin Res Hepatol Gastroenterol 2021;45:101678. Crossref
6. National Institutes of Health, United States Government. Therapeutic management of hospitalized children with MIS-C, plus a discussion on MIS-A. Updated February 2024. Available from: https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-children/hospitalized-pediatric-patients--therapeutic-management-of-mis-c/. Accessed 8 Apr 2024.

The challenge of detecting monoclonal protein in POEMS syndrome: two case reports

Hong Kong Med J 2024 Apr;30(2):170–2 | Epub 15 Apr 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
The challenge of detecting monoclonal protein in POEMS syndrome: two case reports
YN Mew, MB, BS, FHKAM (Medicine)1; YO Lam, MB, BS, FHKAM (Medicine)2; TH Luk, MB, ChB, FHKAM (Medicine)1; KF Hui, MB, ChB, FHKAM (Medicine)2; WC Fong, MB, BS, FHKAM (Medicine)1
1 Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China
2 Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong SAR, China
 
Corresponding author: Dr YN Mew (myn760@hhh.ha.org.hk)
 
 Full paper in PDF
 
 
Case presentations
Case 1
A 60-year-old woman presented to United Christian Hospital in 2019 with a 2-month history of progressive generalised ascending weakness and numbness affecting all four limbs. On clinical examination, she had significant oedema involving her hands and feet. Proximal limb power was full while distal limb power was rated grade 3 on the Medical Research Council scale. Sensory modalities involving pinprick, light touch and proprioception were all diminished distally. She had generalised areflexia. Nerve conduction study revealed markedly reduced motor conduction velocity at 18 to 28 m/s (normal range, >50) in the upper limbs, consistent with demyelination. There was evidence of secondary axonal injury. Limited by significant oedema, lower limb nerve compound muscle action potential and sensory nerve action potential were unrecordable. Cerebrospinal fluid study showed elevated protein level at 899 mg/L with normal white blood cell count. The patient was managed as presumed chronic inflammatory demyelinating polyneuropathy (CIDP). Evaluation of monoclonal gammopathy with serum protein electrophoresis (SPE), urine Bence Jones protein and serum immunoglobulin pattern was unrevealing. Systemic steroid was commenced followed by intravenous immunoglobulin due to disease progression but the patient deteriorated further with distal power grade 0 and became wheelchair bound.
 
Repeated SPE and urine Bence Jones protein test failed to detect any monoclonal gammopathy. Serum free light chain assay of the patient showed persistently raised lambda light chain but normal kappa/lambda ratio. Serum immunofixation was negative. Six months after her initial presentation, positron emission tomography–computed tomography (PET-CT) scan revealed multiple hypermetabolic bony lesions in the skeleton. The dominant lesions were mixed lytic-sclerotic lesions at the left sacrum (maximum standardised uptake value=22.4) and left L5 vertebra (maximum standardised uptake value=16.3). Mild inactive bilateral pleural effusion, pericardial effusion as well as diffuse subcutaneous oedema were also noted. Random trephine bone marrow examination performed at the right iliac crest was unremarkable.
 
At this juncture, the patient developed skin changes with plethora, white nails, flushing, and hypertrichosis of the trunk and limbs (Fig). She was oedematous with orthopnoea and paroxysmal nocturnal dyspnoea. A diagnosis of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) was strongly suspected in view of her polyneuropathy, skin changes, lytic-sclerotic bone lesion, and extracellular volume overload. Plasma vascular endothelial growth factor was checked and was markedly elevated at 370 pg/mL (reference range, <96.2).
 

Figure. Case 1. Skin changes with (a) hyperpigmentation, (b) hypertrichosis, (c) flushing of skin and whitening of nail, and (d) haemangiomata. The patient’s hands and fingers were oedematous as well. (e) Congested chest X-ray with left pleural effusion. (f) Mixed lytic-sclerotic bony lesion at sacrum. The markings were used to aid computed tomography–guided bone biopsy
 
The patient’s fluid overload symptoms deteriorated with respiratory distress. She was oxygen dependent and diuretic therapy was only partially helpful. Therapeutic thoracentesis of the left chest drained 700 mL of transudative fluid. She subsequently underwent CT-guided bone biopsy (Fig). Her sacrum bone biopsy revealed plasmacytoma with lambda light chain restriction. A diagnosis of POEMS was confirmed.
 
Around the same time, DNA from the previous random bone marrow blood was extracted from the patient for immunoglobulin heavy chain and kappa light chain B-cell clonality assay (BIOMED-2 polymerase chain reaction assay). Results revealed clonal gene rearrangement (targeting Vk-Jk segments of immunoglobulin kappa gene) consistent with the presence of a clonal B-cell population.
 
The patient was prescribed a combination of bortezomib, cyclophosphamide and corticosteroid. Oedema resolved first with subsequent improved limb power and dexterity. Her follow-up PET-CT scan after 10 months showed similar bony lesions with reduced metabolic activity.
 
Case 2
A 40-year-old man presented to Queen Elizabeth Hospital in 2013 with progressive generalised oedema. He had had repeated admissions for bilateral lower limb oedema, dyspnoea and orthopnoea. Diuretics were partially helpful. Echocardiogram showed normal left ventricular ejection fraction but evidence of pulmonary hypertension. Serum and urine albumin level was normal. Computed tomography of the thorax and abdomen revealed bilateral pleural effusion, pericardial effusion and ascites. He subsequently developed severe distal limb weakness and became wheelchair bound. Nerve conduction study showed demyelinating sensorimotor polyneuropathy in his upper limbs. Lower limb nerves were unable to be assessed due to severe oedema. The patient developed other features of POEMS with hepatosplenomegaly, papilledema, skin changes with hypertrichosis and acrocyanosis. A PET-CT scan revealed sclerotic bony lesions over the left ilium and multiple thoracic and lumbar vertebral bodies.
 
Similar to Case 1, the patient’s serum and urine were negative for paraprotein. Serum free light chain assay revealed an unremarkable kappa/lambda ratio. Random bone marrow aspiration and trephine biopsy revealed active marrow with mild plasmacytosis. Targeted left iliac bone biopsy showed plasmacytic infiltrates with reversed kappa/lambda ratio. Although plasmacytoma was a concern, there were no definitive histological criteria. Nonetheless based on the highly compatible clinical features of POEMS, he was managed accordingly with cyclophosphamide and corticosteroid. His oedema resolved and he was subsequently able to mobilise with a stick.
 
Discussion
The POEMS is a rare paraneoplastic syndrome caused by plasma cell disorder. Presentation may mimic that of demyelinating polyneuropathy. The diagnostic criteria of POEMS include two mandatory criteria, namely, presence of monoclonal plasma cell disorder of lambda origin and demyelinating polyneuropathy. Major criteria include sclerotic bone lesions, elevated vascular endothelial growth factor, and Castleman disease; minor criteria include skin changes, organomegaly, endocrinopathy, extravascular volume overload, papilledema, thrombocytosis, and polycythemia.1 The diagnosis of POEMS is often delayed. The median time for diagnosis has been reported to be 15 months in a longitudinal cohort of 100 patients, by which time 35% patients had become bed or wheelchair bound.2
 
The above two cases illustrate the difficulty in establishing monoclonal gammopathy even though neurologists and haematologists were alert to the possibility of POEMS. Repeated SPE test, Bence Jones protein test and random bone biopsy were all negative. Plasmacytoma can be demonstrated only on targeted bone biopsy. As a mandatory diagnostic criterion, failure to detect monoclonal gammopathy delays the subsequent management of POEMS. In a large retrospective series, positive monoclonal protein detection on SPE was only 24% to 54%.1
 
Thorough investigations with serum, urine and histological samples are essential. These consist of performing serum protein electrophoresis, immunofixation, serum free light chain assay as well as urine equivalents. Failure to perform immunofixation and serum free light chain analysis may result in missing 30% of POEMS cases.3 Haematological advice and laboratory communication is of utmost importance to exhaust diagnostic means. For Case 1, immunofixation was performed after liaison with the laboratory. A similar situation arises in the United Kingdom where it is a common practice for laboratories to perform immunofixation only if a paraprotein is present in SPE, despite having superior sensitivity.4
 
Non-targeted bone marrow examination carries a high chance of missing the pathology, reflected by a prior case series of six patients in whom three had their pathology missed.5 Image guidance, eg, PET-CT, should be considered in the diagnostic workflow of POEMS. It plays a significant role not only in detecting abnormal bone lesions, but also in increasing diagnostic yield for plasmacytoma in biopsy.
 
Case 1 also illustrates the diagnostic delay of POEMS syndrome partly due to a trial of CIDP treatment, a not uncommon phenomenon. This issue was addressed in a cost-effective analysis of POEMS patients in the United Kingdom.4 The study introduced a diagnostic algorithm incorporating early mandatory vascular endothelial growth factor testing in acquired demyelinating neuropathy patients and helped avoid misdiagnosis and associated healthcare costs.4
 
The two cases are also similar in terms of the debilitation from significant oedema. One should be alert of POEMS when a CIDP patient presents with unexplained oedema. Extravascular volume overload is a common feature of POEMS and can occur in 90% patients, presumably due to a capillary leak phenomenon.1 This includes leg oedema, pleural effusion, pericardial effusion, ascites, papilledema, and asymptomatic pachymeningeal thickening from fluid collection. Presence of oedema in POEMS should not be overlooked as it is a helpful diagnostic clue to differentiate POEMS from CIDP. It also causes significant patient morbidity. Patients may require repeated paracentesis if the oedema remains refractory to diuretics.
 
These two cases illustrate the challenge of establishing monoclonal gammopathy in POEMS. Negative serum and urine paraprotein, immunofixation, serum free light chain assay, or a normal random bone marrow examination do not exclude POEMS and warrant further investigations. We should be aware of the limitation of test methods. Comprehensive clinical assessment, thorough investigations and multidisciplinary communication are essential for early diagnosis and management.
 
Author contributions
Concept or design: YN Mew, WC Fong.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: YN Mew.
Critical revision of the manuscript for important intellectual content: WC Fong, KF Hui.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Acknowledgement
The authors thank Dr Kwan-hung Leung, haematologist at United Christian Hospital, for contributing to patient management.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patients were managed in accordance with the Declaration of Helsinki and provided informed consent for publication.
 
References
1. Dispenzieri A. POEMS syndrome: 2019 update on diagnosis, risk-stratification, and management. Am J Hematol 2019;94:812-27. Crossref
2. Keddie S, Foldes D, Caimari F, et al. Clinical characteristics, risk factors, and outcomes of POEMS syndrome: a longitudinal cohort study. Neurology 2020;95:e268-79. Crossref
3. Keddie S, D’Sa S, Foldes D, Carr AS, Reilly MM, Lunn MP. POEMS neuropathy: optimising diagnosis and management. Pract Neurol 2018;18:278-90. Crossref
4. Marsh ES, Keddie S, Terris-Prestholt F, D’Sa S, Lunn MP. Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs. J Neurol Neurosurg Psychiatry 2021;92:172-6. Crossref
5. Li Y, Valent J, Soltanzadeh P, Thakore N, Katirji B. Diagnostic challenges in POEMS syndrome presenting with polyneuropathy: a case series. J Neurol Sci 2017;378:170-4. Crossref

Acute chorioamnionitis following amnioreduction for polyhydramnios in placental chorioangioma complicating pregnancy: a case report

Hong Kong Med J 2024 Apr;30(2):164–6 | Epub 11 Apr 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Acute chorioamnionitis following amnioreduction for polyhydramnios in placental chorioangioma complicating pregnancy: a case report
Janice TC Leung, MB, ChB; WY Lok, MSc, FHKAM (Obstetrics and Gynaecology); William WK To, MD, FRCOG; CW Kong, MSc, FHKAM (Obstetrics and Gynaecology)
Department of Obstetrics and Gynaecology, United Christian Hospital, Hong Kong SAR, China
 
Corresponding author: Dr CW Kong (melizakong@gmail.com)
 
 Full paper in PDF
 
 
Case presentation
In October 2022, a 29-year-old nulliparous woman at 30 weeks of gestation was found to have a larger-than-dates uterus with symphysial fundal height of 38 cm. Her previous antenatal course had been uneventful with scan at 20 weeks of gestation showing normal fetal morphology and liquor volume. Ultrasound revealed polyhydramnios with amniotic fluid index (AFI) of up to 42 cm but normal fetal growth and morphology. An echogenic lesion measuring 4.7×5.6×4.5 cm3 was seen in the placenta. The lesion had feeding vessels visible on colour flow Doppler and pulsatile flow on pulsed wave Doppler (Fig 1). There were no signs of fetal anaemia or hydrops fetalis. The diagnosis of placental chorioangioma was made. A standard 75-g oral glucose tolerance test was performed due to polyhydramnios and revealed mild gestational diabetes mellitus with normal fasting level (4.7 mmol/L) and marginally raised 2-hour post-loading level of 8.6 mmol/L (normal range for pregnancy, <8.5).
 

Figure 1. Ultrasound images and histological photos of the placental chorioangioma of the patient. (a) A chorioangioma measuring >4 cm inside the placenta. (b) Feeding vessels are seen in the chorioangioma on colour Doppler. (c) The feeding vessel has pulsatile flow on pulsed wave Doppler. (d) The fetal surface of the placenta after delivery showing feeding vessels (arrow) supplying the chorioangioma. (e) The chorioangioma (arrow) and the placental surface of the placenta after delivery. (f) Sectioning of the chorioangioma showing whitish and gelatinous cut surface
 
In view of the severe maternal pressure symptoms with shortness of breath, amnioreduction was performed at 31 weeks of gestation under aseptic technique with continuous ultrasound guidance using a 22-gauge spinal needle connected to low-pressure wall suction. A total of 2280-mL amniotic fluid was drained over 3 hours with post-procedure AFI reduced to 16 cm. In view of the potential risk of preterm labour, a course of betamethasone (12 mg every 24 hours for two doses) was administered intramuscularly prior to amnioreduction to enhance fetal lung maturity. Results of chromosomal microarray studies of the amniotic fluid were normal. One week later, the polyhydramnios recurred with AFI measuring 40 cm. Amnioreduction was repeated at 32 weeks of gestation with 2600-mL amniotic fluid drained over 2.5 hours and AFI reduced to 18 cm. Prophylactic antibiotics were not given prior to either procedure.
 
Three days after amnioreduction, the patient developed signs of sepsis with fever, fetal tachycardia, and abdominal tenderness. Maternal white cell count and C-reactive protein level were elevated. The clinical picture was compatible with acute chorioamnionitis and intravenous antibiotics were commenced. Emergency caesarean section was performed and a baby weighing 2080 g was born with good Apgar score. Septic workup including blood culture, high vaginal swabs, amniotic fluid and placental swabs did not yield any bacterial growth. Both the mother and the baby subsequently recovered well. Histological examination of the placenta confirmed the diagnosis of chorioangioma (Fig 2).
 

Figure 2. Histological slides of the chorioangioma of the patient. (a) Haematoxylin and eosin stain under low-power view (×40) showing nodular proliferation of anastomosing capillaries within a fibromyxoid stroma (arrow is chorionic villi and arrowhead is the chorioangioma). (b) Haematoxylin and eosin staining under high-power view (×200) showing proliferation of anastomosing capillaries lined with endothelial cells (arrow) which is typical for chorioangioma. (c) CD31 immunostaining (a sensitive and specific endothelial marker) under high-power view (×200) highlighting the endothelial cells of the capillaries of the chorioangioma. (d) Haematoxylin and eosin stain under low-power view (×40) showing pale platelet and fibrin deposits alternating with darker red cell-rich layers (arrow) in the chorioangioma
 
Discussion
There are numerous causes for polyhydramnios in singleton pregnancies including gestational diabetes, chromosomal abnormalities, fetal structural abnormalities such as bowel atresia, and placental causes such as chorioangioma. As mild gestational diabetes should not lead to severe polyhydramnios, the most likely primary diagnosis in our patient was chorioangioma. The pathophysiology of polyhydramnios in placental chorioangioma is not completely known. One of the proposed mechanisms is transudation of fluid from the surface of the chorioangioma adjacent to the placental surface. The incidence of placental chorioangioma is estimated to be around 1%. As chorioangiomas >4 cm can lead to complications including polyhydramnios, preterm delivery, intrauterine growth restriction, hydrops fetalis and even fetal demise, close ultrasound surveillance, intrauterine interventions or even early delivery may be necessary.1 Careful ultrasound examination of the placenta is warranted for all cases of gross polyhydramnios.
 
Amnioreduction has been commonly performed to relieve polyhydramnios in both singleton and multiple pregnancies. Traditionally, amniodrainage would be performed using an 18-to 22-gauge spinal needle with the amniotic fluid removed manually using a three-way tap and 50-mL syringe. The use of wall suction and a vacuum bottle aspiration system connected to a needle has been proposed in recent years to speed up the procedure and reduce operator fatigue.2
 
Different complications including preterm labour, prelabour rupture of membranes and placental abruption have been reported following amnioreduction. There is no consensus or guideline for the most appropriate size of needle or the rate at which amniotic fluid can be safely removed. Rapid drainage using an 18- or 20-gauge needle connected to the vacuum system with the fastest rate of drainage up to 178 mL/min has been advocated by Leung et al2 since 2004. The overall complication rate for this rapid drainage, including placental abruption, prelabour rupture of membranes and fetal bradycardia in singleton and multiple pregnancies, was 3.1%.2 Placental abruption has been reported following amnioreduction for polyhydramnios specifically caused by chorioangioma. One patient has been reported in whom two episodes of amnioreduction were performed a few days apart using an 18-gauge needle connected to a vacuum system.3 With an average drainage rate of 100 mL/min, 2500 mL and 2700 mL of amniotic fluid was removed. Placental abruption occurred 12 hours after the second amnioreduction. The authors concluded that caution should be exercised when performing large-volume or rapid amnioreductions in idiopathic or chorioangioma-associated polyhydramnios.3 We used a small needle (22-gauge) to drain the amniotic fluid slowly at a rate of 12.7 mL/min in our first amnioreduction and 17.3 mL/min in the second amnioreduction in an attempt to lower the risk of placental abruption and preterm prelabour rupture of membranes.
 
Erfani et al4 recently evaluated the complications following amnioreduction in singleton pregnancies without other interventions by combining their findings with those of six other studies. The incidence of preterm labour was 50.5% (48/95) and that of placental abruption was 1.3% (4/315), although there was no acute chorioamnionitis in a total of 244 patients.4 This implies that the role of prophylactic antibiotics is dubious. Nonetheless not all studies specified the duration of the amnioreductions. Only one case of acute chorioamnionitis following amnioreduction has been reported.5 That patient had a twin pregnancy with polyhydramnios not caused by twin-twin transfusion syndrome. Amnioreduction was performed at 31 weeks of gestation using an 18-gauge needle with a total of 1950-mL amniotic fluid removed at a rate of 65 mL/min. She developed acute chorioamnionitis 18 hours following the procedure.5 Although it is logical to deduce that the risk of chorioamnionitis will increase with the length of procedure for amnioreduction, there are no relevant studies available in the literature to support this association due to the rarity of this complication.
 
As far as we are aware, this is the second case reported in the literature of acute chorioamnionitis following amnioreduction. As caesarean section was performed immediately under antibiotic cover when the patient developed signs of sepsis, the septic workup did not yield any bacterial growth.
 
It is crucial to maintain a high index of suspicion and search for placental chorioangioma in a fetus where there is no obvious cause for polyhydramnios to ensure prompt diagnosis and proper management. Amnioreduction carries risks of complications, including placental abruption and acute chorioamnionitis, and the optimal rate of drainage remains controversial.
 
Author contributions
Concept or design: JTC Leung, CW Kong.
Acquisition of data: JTC Leung.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: JTC Leung, CW Kong.
Critical revision of the manuscript for important intellectual content: WWK To, CW Kong.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Acknowledgement
The authors thank Dr CL Ho from the Department of Pathology of United Christian Hospital for the histological slides of the chorioangioma of the patient.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. Written consent was obtained from the patient for publication of this article and the accompanying images.
 
References
1. Buca D, Iacovella C, Khalil A, et al. Perinatal outcome of pregnancies complicated by placental chorioangioma: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2020;55:441-9. Crossref
2. Leung WC, Jouannic JM, Hyett J, Rodeck C, Jauniaux E. Procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios. Ultrasound Obstet Gynecol 2004;23:154-8. Crossref
3. Kim A, Economidis MA, Stohl HE. Placental abruption after amnioreduction for polyhydramnios caused by chorioangioma. BMJ Case Rep 2018;2018:bcr2017222399. Crossref
4. Erfani H, Diaz-Rodriguez GE, Aalipour S, et al. Amnioreduction in cases of polyhydramnios: indications and outcomes in singleton pregnancies without fetal interventions. Eur J Obstet Gynecol Reprod Biol 2019;241:126-8. Crossref
5. Elliott JP, Sawyer AT, Radin TG, Strong RE. Large-volume therapeutic amniocentesis in the treatment of hydramnios. Obstet Gynecol 1994;84:1025-7.

Burkholderia pseudomallei pericarditis as a mimicker of tuberculous pericarditis: a case report

Hong Kong Med J 2024 Apr;30(2):167–9 | Epub 17 Apr 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Burkholderia pseudomallei pericarditis as a mimicker of tuberculous pericarditis: a case report
Frederick HC Lau, MB, BS; MF Lin, MB, BS, FHKAM (Surgery); WS Ng, MB, BS, FHKAM (Surgery)
Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, Hong Kong SAR, China
 
Corresponding author: Dr Frederick HC Lau (hcf.lau@ha.org.hk)
 
 Full paper in PDF
 
 
Introduction
Melioidosis, also known as Whitmore’s disease, occurs predominantly in tropical climates and can cause pneumonia, soft tissue infection, brain abscess, and septicaemia. Very few cases of melioidosis pericarditis have been reported. The most common cause of constrictive pericarditis in Hong Kong is tuberculosis. We report a patient with melioidosis constrictive pericarditis with presentation mimicking tuberculous pericarditis infection in whom we performed pericardiectomy.
 
Case presentation
A 61-year-old man who was a chronic smoker and worked on a construction site presented with fever and heart failure symptoms including dyspnoea, orthopnoea, and ankle oedema. Laboratory results showed elevated white blood cell count (21.7 × 109/L) with neutrophils predominant (19 × 109/L) and raised levels of C-reactive protein (303 mg/L) and liver parenchymal enzymes (alanine transaminase level: 153 U/L, alkaline phosphate level: 125 U/L). Repeated blood cultures were negative. Sputum for acid-fast bacilli smear and culture and Mycobacterium tuberculosis polymerase chain reaction were negative. Computed tomography (CT) with contrast showed bilateral multiple small lung nodules (largest 1.3 cm) with mediastinal and right hilar lymphadenopathy. Transthoracic echocardiogram revealed bilateral pleural effusion with pericardial effusion requiring pericardial drain insertion 2 days after admission. Analysis of pericardial fluid showed elevated adenosine deaminase (ADA) level (58 U/L) and culture showed scanty growth of pseudomonal species after 6 days. No Mycobacterium species was isolated after 6 weeks of incubation. The patient was commenced on empiric antituberculosis treatment (isoniazid 300 mg daily, rifampicin 600 mg daily, pyrazinamide 1500 mg daily, ethambutol 900 mg daily, and pyridoxine 20 mg daily) 3 weeks after admission in view of the elevated ADA level, persistent intermittent fever while on intravenous piperacillin/tazobactam and due to the risk of tuberculous pericarditis in Hong Kong. He was discharged and referred to our cardiothoracic centre for elective pericardial biopsy.
 
While waiting for our outpatient clinic assessment, the patient was admitted as an emergency 1 month after commencing antituberculosis treatment with shortness of breath and frequent episodes of atrial flutter. He was later transferred to our cardiothoracic unit for further management. Echocardiogram and CT scan of the thorax showed a large heterogeneous pericardial collection with adhesions and internal echogenicities of up to 3.5 cm in diameter, located next to the left ventricle with signs of compression and constriction (Fig 1). There were also signs of septal bounce and exaggerated respirophasic changes of tricuspid and mitral inflow. Left and right ventricular systolic function was reduced due to impaired bi-ventricular contractility caused by pericardial adhesions and constriction, confirmed by right heart catheterisation (high right ventricular end-diastolic pressure–to–right ventricular systolic pressure ratio, discordance between left ventricular systolic pressure and right ventricular systolic pressure during respiration).
 

Figure 1. Preoperative computed tomography scan of the thorax showing pericardial collection with adhesions and internal echogenicities (a), leading to compression and constriction of the left ventricle (b)
 
Pericardiectomy was performed and the excised pericardium sent for sectioning revealed suppurative granulomatous inflammation (Fig 2). The Ziehl–Neelsen stain and Mycobacterium tuberculosis polymerase chain reaction were negative. Pericardial pus aspirate contained Burkholderia pseudomallei species.
 

Figure 2. Intraoperative photo during pericardiectomy. Thick yellowish material was expressed after pericardium incision
 
Antituberculosis treatment was withheld and melioidosis was treated with intravenous meropenem for 4 weeks and oral co-trimoxazole with doxycycline as maintenance therapy. The patient’s postoperative course was uneventful. Postoperative CT of the thorax at 3 months showed reduced pericardial effusion, decreased lung consolidation, and reduced pleural effusion.
 
Discussion
Melioidosis is caused by intracellular Gram-negative saprophytic B pseudomallei. This bacterium was formerly classified in the genus Pseudomonas but is now separated from Pseudomonas and Stenotrophomonas. It is predominantly found in contaminated water and soil and spread to humans through direct contact with contaminated sources. Melioidosis is a multiorgan infectious disease with pneumonia as the most common presentation. A progressive increase in the number of cases has been observed in Hong Kong over the last 20 years, as well as in Asia over the past decade.1 There was no previous reported case of melioidosis pericarditis in Hong Kong.1
 
Tuberculosis is caused by the acid-fast bacillus M tuberculosis. It is airborne and primarily affects the lungs, and is common in Southeast Asia. The level of ADA, an enzyme in lymphocytes, increases in the presence of inflammatory effusions caused by bacterial infection, granulomatous inflammation, malignancy, and autoimmune disease. It is typically higher in effusions caused by tuberculosis than those caused by other conditions with a level >40 U/L in lymphocyte-predominant effusions having a sensitivity of 87% to 93% and a specificity of 89% to 97% for tuberculosis.2 Nonetheless in neutrophil-predominant effusions, ADA level may lead to false-positive results since ADA is normally elevated.2
 
Constrictive pericarditis is a disease characterised by pericardial effusion with constrictive pathology. The most common cause is idiopathic, followed by tuberculosis, or post-irradiation and post-pericardiotomy. It is characterised by echocardiography findings of septal bounce, diastolic shift of the interventricular septum, restrictive left ventricular filling pattern, and cardiac catheterisation finding of square root sign.3
 
The presentation, laboratory results and imaging findings are very similar for melioidosis and tuberculous pericarditis. Most patients have a subacute-to-chronic disease course. The protein, sugar and white cell count of pericardial fluid may also be similar in both diseases. Compared with patients with tuberculous pericarditis, those with melioidosis pericarditis more often have a neutrophil-predominant white blood cell count,4 as in our case. Histological findings can show granulomatous inflammation with tuberculosis showing a caseous type.5
 
It is important to differentiate between B pseudomallei and M tuberculosis and make a correct diagnosis since the treatment for melioidosis pericarditis and tuberculous pericarditis varies markedly. A prolonged course of intravenous ceftazidime followed by a combination of co-trimoxazole and doxycycline is prescribed for melioidosis while a prolonged course of rifampicin, ethambutol, pyrazinamide and isoniazid is prescribed for tuberculosis.3 An incorrect diagnosis not only delayed treatment for melioidosis in our patient with consequent worsening of his clinical condition, but may also have caused more harm by exposing the patient to the side-effects of tuberculosis treatment. It is important to send pericardial fluid for culture and to look meticulously for the two organisms.
 
Conclusion
The presentation, laboratory results and imaging findings can be very similar for melioidosis and tuberculous pericarditis. It is important to bear this in mind during investigations for chronic pericarditis and obtain pericardial culture. This will ensure prompt diagnosis and timely commencement of appropriate treatment.
 
Author contributions
All authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided informed consent for all treatments and procedures, and consent for publication.
 
References
1. Lui G, Tam A, Tso YK, et al. Melioidosis in Hong Kong. Trop Med Infect Dis 2018;3:91. Crossref
2. Chau E, Sarkarati M, Spellberg B. Adenosine deaminase diagnostic testing in pericardial fluid. JAMA 2019;322:163-4. Crossref
3. Chow CY, Lun KS. Idiopathic effusive constrictive pericarditis in an adolescent boy: a rare cause of heart failure with diagnostic difficulty. Hong Kong J Paediatr (new series) 2015;20:110-4.
4. Chetchotisakd P, Anunnatsiri S, Kiatchoosakun S, Kularbkaew C. Melioidosis pericarditis mimicking tuberculous pericarditis. Clin Infect Dis 2010;51:e46-9. Crossref
5. Wong KT, Puthucheary SD, Vadivelu J. The histopathology of human melioidosis. Histopathology 1995;26:51-5. Crossref

Successful endovascular treatment in a COVID-19 patient with mycotic aortoiliac aneurysm due to Salmonella typhi: a case report

Hong Kong Med J 2024 Feb;30(1):72–4 | Epub 8 Feb 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Successful endovascular treatment in a COVID-19 patient with mycotic aortoiliac aneurysm due to Salmonella typhi: a case report
Samuel Edrei So, MB, BS; YC Chan, MB, BS, FRCS; Stephen W Cheng, MB, BS, FRCS
Division of Vascular Surgery, Department of Surgery, Queen Mary Hospital, Hong Kong SAR, China
 
Corresponding author: Dr YC Chan (ycchan88@hku.hk)
 
 Full paper in PDF
 
 
Introduction
Conventional surgical options for mycotic aneurysm include ligation or excision with in situ or extra-anatomical reconstruction. Endovascular stenting in the presence of sepsis is controversial but may be the preferred management for critically ill patients who are deemed very high risk for open intervention.1 Mycotic aneurysms due to Salmonella typhi are extremely rare, with only two cases described in the literature.2
 
We report a coronavirus disease 2019 (COVID-19)–positive patient who presented with severe abdominal pain and back pain and who was subsequently diagnosed with a mycotic aortoiliac aneurysm. Repeated blood and stool cultures yielded S typhi. He was successfully treated with endovascular stent graft repair and by postoperative long-term antibiotics.
 
Case presentation
A 56-year-old frail malnourished man with a history of diabetes mellitus presented with a 3-week history of progressively worsening malaise and abdominal and back pain. He had a fever of 38.1°C. Clinical examination revealed tenderness over the central and left lower quadrant of the abdomen. Initial blood tests noted a haemoglobin level of 13.5 g/dL and an elevated total white cell count at 13.58 × 109. Chest radiograph was unremarkable, but emergency computed tomography scan demonstrated a saccular aortoiliac aneurysm involving the distal aorta and the left common iliac artery (Fig a and b). Blood cultures were repeatedly positive for S typhi. The patient was also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission screening necessitating patient isolation.
 

Figure. (a and b) Emergency computed tomography (CT) showing the mycotic aneurysm involving the aortoiliac arteries (arrows). (c) Intraoperative angiogram showing the enlarging aortoiliac aneurysm (arrow), successfully excluded following embolisation of the left internal iliac artery and external iliac artery, with deployment of an aorto-uni-iliac stent graft (d). Follow-up CT at 1 month (e) and 3 months (f) postoperatively showing successful thrombosis and endovascular exclusion of the mycotic aneurysm
 
Infection control specialists and microbiologists were consulted for multidisciplinary management. The patient was started on intravenous meropenem, and fever resolved after 24 hours. Nonetheless in view of persistent symptoms, emergent endovascular intervention was performed 3 days following admission. Angiogram confirmed the position and extent of the mycotic aneurysm (Fig c). The aortic bifurcation was narrow (14.6 mm × 10.8 mm) and the aortic diameter was small at 16 mm. Thus, we opted to use an aorto-uni-iliac stent graft (Endurant II; Medtronic, Galway, Ireland). The distal end of the stent graft was deployed at the distal right common iliac artery. The left internal iliac artery was embolised with a 6 mm × 20 mm coil (Interlock detachable coils; Boston Scientific, Marlborough [MA], US), and the left external iliac artery with an Amplatzer vascular plug (Abbott, Abbott Park [IL], US). The left lower limb was revascularised with a femoral-femoral bypass using a 7-mm ringed polytetrafluoroethylene vascular graft (Advanta VXT; Getinge, Gothenburg, Sweden). Completion angiogram showed successful exclusion of the aortic and left common iliac artery aneurysm (Fig d). The patient’s discomfort improved. He was prescribed intravenous meropenem for 6 weeks followed by lifelong oral azithromycin based on culture sensitivity results and the recommendation of microbiologists. Follow-up computed tomography scan at 1 month (Fig e) and 3 months (Fig f) postoperatively showed thrombosis and successful endovascular exclusion of the mycotic aneurysm.
 
Discussion
To the best of our knowledge this is the first published case of a COVID-19–positive patient with S typhi aortoiliac mycotic aneurysm. Salmonella typhi is responsible for typhoid fever that is still endemic in some South Asian and African countries. Symptoms are primarily gastrointestinal with nausea and diarrhoea but extraintestinal complications such as aortitis and endocarditis may occur in the elderly or immunocompromised individuals.3
 
Salmonella typhi is an exceedingly rare cause of mycotic aneurysm. Only one previous report has suggested the bacteria as a culprit. Guo et al2 showed that most Salmonella mycotic aneurysms were caused by non-typhoidal Salmonella species such as Salmonella enteritidis (30%) and Salmonella choleraesuis (20%) with S typhi responsible for only 2% of cases in this cohort. The exact mechanism of typhoid-related aortic infection is unknown, but possibilities include bacteraemia following bacterial invasion of the gut mucosa, with seeding to the aortic wall and subsequent aneurysmal degeneration. Gallstones may provide a nidus for persistent infection with possible contiguous spread to nearby vasculature. The persistence of S typhi in mesenteric lymph nodes may contribute to relapsing typhoid fever, resulting in disseminated infection long after the initial presentation.4 Presumably, the presence of S typhi in the para-aortic and para-iliac lymph nodes could erode to the surrounding blood vessels with subsequent aneurysm development.
 
Our patient was noted to be positive for SARS-CoV-2 (ie, COVID-19 positive) during routine admission screening. This may have important implications in the pathogenesis, diagnosis and subsequent management of many diseases. Due to the ubiquitous spread of the virus, there have been increasing reports of concurrent infection of SARS-CoV-2 with local endemic pathogens. A case report in 20215 documented co-infection with both SARS-CoV-2 and S typhi in a 14-year-old boy returning to Canada from Pakistan. This case report concluded that since the potential presentation of both disease entities would include fever and gastrointestinal disturbance, the presence of COVID-19 may have confounded the diagnosis of other infections for clinicians unfamiliar with typhoid fever. This diagnostic bias has also been observed in countries where typhoid fever is endemic with cases of early typhoid fever initially treated as COVID-19 infection. This resulted in a delay in prescribing appropriate antibiotic treatment and possible progression to life-threatening complications such as intestinal perforation.6 The co-epidemic of COVID-19 and S typhi in some Asian countries placed a heavy burden on local health care resources. Insufficient medical resources combined with delayed diagnosis and treatment contributed to increased mortality from typhoid fever in patients who may previously have made an uneventful recovery.
 
Co-infection with SARS-CoV-2 and S typhi may contribute to the pathogenesis and progression of mycotic aneurysm. The relationship between SARS-CoV-2 and mycotic aneurysms may be explained by the immunosuppressive as well as pro-inflammatory effects of COVID-19 infection. Tian et al7 demonstrated that SARS-CoV-2 caused immunosuppression in the early stages of infection via suppression of chemokine signalling and immune cell response. In our patient, immunosuppression due to diabetes mellitus and recent COVID-19 infection may have resulted in increased risk of bacterial seeding and colonisation of the aorta. Contemporary literature also suggests that COVID-19 may contribute to aneurysmal development by upregulation and elaboration of proinflammatory mediators and chemokines by binding to angiotensin-converting enzyme 2 receptors on host cells.8 Current concepts of SARS-CoV-2 infection and aneurysm pathogenicity suggest that COVID-19 may theoretically augment progression of aneurysms, the impact of which may become clearer as the pandemic progresses.
 
Open operative management of mycotic aneurysm has been gradually replaced by endovascular options, with many studies demonstrating effectiveness and durability of the latter.9 Riley and Teixeira10 documented long-term durability of endovascular intervention in infected pseudoaneurysms. In our patient, we were able to successfully exclude the aneurysm with an endovascular approach, but long-term follow-up and surveillance imaging is essential to guarantee durability. In terms of his COVID-19 infection, the patient did not develop any respiratory symptoms nor were any abnormalities noted on chest radiographs, and no specific therapy was provided.
 
In conclusion, typhoid fever remains a major worldwide public health concern. This is the first case in the world’s contemporary literature of a S typhi mycotic aortoiliac aneurysm in a patient infected with COVID-19. This report emphasises the importance of early tertiary vascular referral and prompt multidisciplinary management involving microbiologists, infection control specialists, and vascular surgeons. We were able to control the sepsis with timely endovascular treatment yielding good mid-term results. Although the global situation regarding COVID-19 is improving and our understanding of COVID-19 is increasingly well developed, this case report aims to raise awareness among readers about the possible impact of COVID-19 on the diagnosis, presentation, and development of other pathologies.
 
Author contributions
Concept or design: YC Chan.
Acquisition of data: SE So.
Analysis or interpretation of data: SE So.
Drafting of the manuscript: SE So.
Critical revision of the manuscript for important intellectual content: YC Chan, SW Cheng.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have declared no conflicts of interests.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided informed written consent to publication of this report.
 
References
1. Taylor PR, Chan YC. Endovascular treatment in the management of mycotic aortic aneurysms. In: Thompson MM, Morgan RA, Matsumara JS, Sapoval M, Loftus I, editors. Endovascular Intervention for Vascular Disease. Principles and Practice. London: Informa Healthcare; 2008: 235-41.
2. Guo Y, Bai Y, Yang C, Wang P, Gu L. Mycotic aneurysm due to Salmonella species: clinical experiences and review of the literature. Braz J Med Biol Res 2018;51:e6864. Crossref
3. Griffin AJ, Li LX, Voedisch S, Pabst O, McSorley SJ. Dissemination of persistent intestinal bacteria via the mesenteric lymph nodes causes typhoid relapse. Infect Immun 2011;79:1479-88. Crossref
4. Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis 2001;32:263-9. Crossref
5. Ayoubzadeh SI, Isabel S, Coomes EA, Morris SK. Enteric fever and COVID-19 co-infection in a teenager returning from Pakistan. J Travel Med 2021;28:taab019. Crossref
6. Abdul Aziz JM, Abdullah SK, Al-Ahdal TM, et al. Diagnostic bias during the COVID-19. A rare case report of Salmonella typhi. Ann Med Surg (Lond) 2022:74:103282. Crossref
7. Tian W, Zhang N, Jin R, et al. Immune suppression in the early stage of COVID-19 disease. Nat Commun 2020;11:5859. Crossref
8. Xu B, Li G, Guo J, et al. Angiotensin-converting enzyme 2, coronavirus disease 2019, and abdominal aortic aneurysms. J Vasc Surg 2021;74:1740-51. Crossref
9. Sörelius K, Mani K, Björck M, et al. Endovascular treatment of mycotic aortic aneurysms: a European multicenter study. Circulation 2014;130:2136-42. Crossref
10. Riley CJ, Teixeira P. Development of symptomatic inflammatory aneurysm treated with endovascular repair in coronavirus disease 2019–infected patient. J Vasc Surg Cases Innov Tech 2021;7:193-6. Crossref

High-dose N-acetylcysteine in an immunocompromised patient with COVID-19: a case report

Hong Kong Med J 2024 Feb;30(1):69–71 | Epub 8 Feb 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
High-dose N-acetylcysteine in an immunocompromised patient with COVID-19: a case report
KY Lai, FHKAM (Medicine), FRCP1; SY Au, FHKAM (Medicine), FRCP2; KC Sin, FHKAM (Medicine), FRCP1; SK Yung, FHKAM (Medicine), FRCP1; Anne KH Leung, FHKAM (Anaesthesiology), FJFICM1
1 Department of Intensive Care, Queen Elizabeth Hospital, Hong Kong SAR, China
2 Cardiovascular Centre, St Paul's Hospital, Hong Kong SAR, China
 
Corresponding author: Dr SY Au (h0145237@gmail.com)
 
 Full paper in PDF
 
 
Case presentation
On 19 June 2022, a 45-year-old man was admitted to intensive care unit with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. His body mass index was 22.3. He had a history of hypertension, diabetes mellitus, hyperlipidaemia, and immunoglobulin A nephropathy. He had been receiving prednisolone and mycophenolate mofetil following a renal transplant. His baseline creatinine level was 203 μmol/L. Three doses of CoronaVac vaccine had failed to induce an antibody response.
 
The patient was in septic shock and had respiratory failure and acute renal failure. He had myopericarditis with elevated level of serum troponin I, diffuse ST elevation on electrocardiogram, and impaired left ventricular ejection fraction of 40% on echocardiogram. Coronary angiogram on 21 June 2022 was normal and myocardial biopsy revealed increased interstitial macrophages. Urine contained Enterococcus faecalis but no white blood cells on microscopy. Screening for other bacterial, viral or fungal co-infections was negative. He was prescribed intravenous remdesivir 200 mg once followed by 100 mg every 12 hours for four more doses and intravenous hydrocortisone 100 mg every 8 hours, and the nephrologist discontinued his mycophenolate mofetil treatment. He received broad spectrum antibiotics as directed by infectious disease specialists. Enoxaparin 60 mg was administered subcutaneously every 48 hours for prophylaxis of deep vein thrombosis. Infectious disease specialists did not recommend tocilizumab, baricitinib, monoclonal antibodies, or convalescent plasma.
 
The patient received intravenous high-dose N-acetylcysteine at a dose appropriate for treatment of paracetamol overdose as treatment of influenza-induced cytokine storm. Animal studies have shown that an oral dose of N-acetylcysteine 1 g/kg/day improved the survival of mice with otherwise lethal influenza infection and was synergistic with oseltamivir with an endpoint survival of 100%.1 Human oral availability of N-acetylcysteine is 6% to 10%. We have reported previously successful treatment of a patient with 2009 H1N1 influenza virus pneumonia with N-acetylcysteine, administered as a 100 mg/kg continuous intravenous infusion daily for 3 days, with consequent suppression of fever and C-reactive protein concentration and corresponding clinical improvement.2 The C-reactive protein of this patient reduced from 183 mg/L to 11.7 mg/L and fraction of inspired oxygen requirement from 1.0 to 0.35. The positive end expiratory pressure reduced from 18 cm H2O to 10 cm H2O. Nonetheless the patient experienced a relapse of cytokine storm and pulmonary deterioration following discontinuation of high-dose N-acetylcysteine therapy before viral clearance. The C-reactive protein rebounded to 132 mg/L and fraction of inspired oxygen requirement increased to 0.85 and positive end expiratory pressure requirement to 16 cm H2O. Results for sepsis workup were negative. The patient responded to reintroduction of N-acetylcysteine therapy and showed no relapse of cytokine storm when it was discontinued after viral clearance.2 The patient, with SARS-CoV-2 pneumonia, received an infusion of N-acetylcysteine 10 g in 500-mL 5% dextrose solution at 21 mL/hour for 2 days from 21 June 2022. C-reactive protein level reduced from 278 mg/L to 72 mg/L and procalcitonin level from >200 ng/mL to 33.33 ng/mL. Fraction of inspired oxygen requirement decreased from 0.6 to 0.35 and positive end expiratory pressure requirement from 10 cm H2O to 6 cm H2O over 2 days following high-dose N-acetylcysteine infusion. When the patient showed no signs of viral clearance on 26 June 2022 and antibodies against SARS-CoV-2 remained negative, we commenced maintenance treatment with N-acetylcysteine at 2.5 g in 250 mL 5% dextrose solution infused over 4 hours twice daily (100 mg/kg/day) from 26 June 2022 until viral clearance on 18 July 2022. The patient was weaned off inotropic agents and mechanical ventilation and became dialysis and oxygen supplement independent. He was discharged from the intensive care unit on 29 June 2022 and resumed immunosuppressive therapy on 30 June 2022. He was discharged home on 28 July 2022. The patient failed to develop any antibody response against SARS-CoV-2 throughout the infection (Fig).
 

Figure. Schematic diagram for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–induced cytokine storm: Invasion of susceptible human cell by SARS-CoV-2 leads to the production of SARS-CoV-2 proteins in the endoplasmic reticulum (ER). The accumulation of SARS-CoV-2 proteins inside the ER induces the production of reactive oxygen species (ROS) through the ER-overload response, which in turn leads to the activation of nuclear factor–kappa B (NF-κB) and the production of pro-inflammatory cytokines. High-dose N-acetylcysteine (NAC) antioxidant therapy prevents the SARS-CoV-2–induced cytokine storm by suppressing ROS and NF-κB activation
 
Discussion
The SARS-CoV-2 mutates rapidly and relies on host cell factors and physiological processes for its entry, replication, and egress. These processes result in cytopathic damage, cytokine dysregulation, and death of host cells. These non-mutable key steps inside the host may be novel targets for future therapeutic strategies against these rapidly mutating viruses. The endoplasmic reticulum (ER) stores the majority of calcium ions and governs protein translation. The accumulation of proteins in the ER membrane, namely ER overload, leads to release of calcium ions from the ER and production of reactive oxygen species. This results in the activation of nuclear factor–kappa B (NF-κB) and the release of pro-inflammatory cytokines. The accumulation of coronavirus spike protein in the ER membrane results in an ER-overload response and cytokine storm.3 Open reading frame 3a (ORF3a) protein, ORF7a protein, membrane protein, and nucleocapsid protein of SARS-CoV-2 are also NF-κB activators. Of these four, ORF7a protein is the most potent NF-κB inducer and pro-inflammatory cytokine producer.4 N-acetylcysteine is an antioxidant against reactive oxygen species and is a potent NF-κB inhibitor.5 Oral N-acetylcysteine administered at 600 mg thrice daily has been shown to reduce mortality in hospitalised SARS-CoV-2 patients.6 The clinical course of our patient suggests that high-dose N-acetylcysteine antioxidant therapy was able to control the cytokine storm of SARS-CoV-2 infection.
 
The SARS-CoV-2 virus mutates rapidly to produce new variants that can evade human antibody response and escape T-cell recognition and clearance. New variants cause challenges to the global effort in developing effective vaccines and medications against SARS-CoV-2. Current therapeutic strategies including vaccination, anti-viral medications, and monoclonal antibodies are directed against the mutable targets of SARS-CoV-2. The SARS-CoV-2 vaccines and monoclonal antibodies that are highly effective against the SARS-CoV-2 wild-type (Wuhan-Hu-1) strain failed to confer adequate protection against the breakthrough infection nor prevent antibody evasion of omicron variants. Nonetheless high-dose N-acetylcysteine therapy acts directly against the reactive oxygen species and NF-κB activation in the ER-overload response of the host, independent of viral mutation. N-acetylcysteine has a complementary or even synergistic role to therapeutic agents that act on the mutable targets of SARS-CoV-2.
 
This case report illustrates that high-dose N-acetylcysteine can protect against SARS-CoV-2–induced cytokine storm in an immunocompromised host who could not elicit an antibody response. By controlling the cytokine storm, this patient coexisted with SARS-CoV-2 until viral clearance. As of 16 October 2022, only 23.3% of people in low-income countries had received at least one dose of coronavirus disease 2019 vaccine. If the protection afforded by high-dose N-acetylcysteine against severe complications of SARS-CoV-2 infection in patients without antibody response can be confirmed in prospective studies, non-fully vaccinated people and those with suboptimal antibody response to vaccination may benefit. This may include those with malignancies, on chemotherapy or immunosuppressive medications, with inborn errors of immunity, or with autoantibodies against type I interferons who are prone to critical SARS-CoV-2 pneumonia. N-acetylcysteine is safe and a category B drug for pregnancy. It is affordable for countries with limited resources and has the potential to end the coronavirus disease 2019 pandemic.
 
Author contributions
Concept or design: KY Lai.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: KY Lai, SY Au.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have declared no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided informed consent for all treatments and procedures, and consent for publication.
 
References
1. Ungheri D, Pisani C, Sanson G, et al. Protective effect of N-acetylcysteine in a model of influenza infection in mice. Int J Immunopathol Pharmacol 2000;13:123-8.
2. Lai KY, Ng WY, Chan PK, Wong KF, Cheng F. High-dose N-acetylcysteine therapy for novel H1N1 influenza pneumonia. Ann Intern Med 2010;152:687-8. Crossref
3. Versteeg GA, van de Nes PS, Bredenbeek PJ, Spaan WJ. The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. J Virol 2007;81:10981-90. Crossref
4. Su CM, Wang L, Yoo D. Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2. Sci Rep 2021;11:13464. Crossref
5. Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology 2021;29:91-100. Crossref
6. Izquierdo JL, Soriano JB, González Y, et al. Use of N-acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19. Sci Prog 2022;105:368504221074574. Crossref

Common carotid artery pseudoaneurysm secondary to erosion by an oesophageal stent: a case report

Hong Kong Med J 2024 Feb;30(1):66–8 | Epub 8 Jan 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Common carotid artery pseudoaneurysm secondary to erosion by an oesophageal stent: a case report
SC Tam, FRCSEd, FHKAM (Surgery); Albert CW Ting, MS, FRCS; Stephen WK Cheng, MS, FRCSEd
Department of Surgery, Queen Mary Hospital, Hong Kong SAR, China
 
Corresponding author: Dr SC Tam (tsc587@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentation
A 59-year-old woman had inoperable carcinoma of the upper oesophagus and had undergone chemoradiotherapy and immunotherapy. A covered oesophageal stent (Niti-S, 20 mm in diameter, 80 mm in length; Taewoong Medical, South Korea) was inserted in August 2021 to manage a tracheoesophageal fistula. The proximal end of the stent was located just distal to the cricopharyngeal constriction. Five months after stent placement, the patient developed erosions at the proximal and distal ends of the stent into the trachea and bronchi, respectively. A covered tracheal stent (AERO, 18 mm in diameter, 40 mm in length; Merit Medical, South Jordan [UT], US) and a distal extension with a covered oesophageal stent (Niti-S) were inserted on two separate occasions.
 
The patient presented to the emergency department 7 months after initial oesophageal stent insertion with haemoptysis. Her haemoglobin level had fallen to 6.3 g/dL and she developed hypotension and desaturation requiring intubation and admission to the intensive care unit. Upper endoscopy revealed blood clots over the proximal part of the oesophagus but no active bleeding following clot removal. Computed tomography showed no contrast extravasation. The upper end of the oesophageal stent was close to the left common carotid artery. A small suspicious outpouching of the artery was also seen at that location (Fig 1a and 1b).
 

Figure 1. (a) Axial image, (b) three-dimensional reconstruction image, and (c) on-table digital subtraction angiography image showing close proximity of the upper part of oesophageal stent and left common carotid artery. A small outpouching from the carotid artery raises the suspicion of a carotid pseudoaneurysm (red arrows)
 
Surgery was performed under general anaesthesia via a left neck incision. Retrograde puncture of the left common carotid artery was performed and an 8-Fr vascular sheath (AVANTI+; Cordis, Miami Lakes [FL], US) was placed. Digital subtraction angiogram revealed a small pseudoaneurysm confirming our clinical suspicion (Fig 1c). Oesophageal stent erosion was suspected to be the cause due to its proximity. Complete exclusion of the pseudoaneurysm was achieved (Fig 2) using a covered vascular stent (Covera Plus, 8 mm in diameter, 60 mm in length; Becton, Dickinson and Company, Franklin Lakes [NJ], US).
 

Figure 2. (a) Completion angiogram showing complete exclusion of pseudoaneurysm following deployment of a covered vascular stent. (b) Reassessment computed tomography showing relationship between all stents in the carotid artery and aerodigestive tract
 
Postoperatively, the patient’s condition improved with no rebleeding. She refused further surgery to repair the fistula via a manubrial resection. Further covered tracheal stenting (Dumon Y, 15 mm in diameter; Boston Medical Products Inc, Shrewsbury [MA], US) was performed to exclude residual tracheoesophageal fistula and prevent aspiration pneumonia. The patient was prescribed long-term moxifloxacin because of the potential communication with the aerodigestive tract and contamination. She was well 6 weeks later. Reassessment computed tomography showed a patent carotid stent with no features of stent infection and no residual pseudoaneurysm.
 
Discussion
Upper gastrointestinal bleeding is a frequent presentation following oesophageal stenting. Endoscopy has both diagnostic and therapeutic roles in common bleeding pathologies such as tumour and peptic ulcer. The presence of a stent often makes identification of a bleeding site difficult. Diagnosing fistulation with major arteries requires a high level of suspicion, especially if the bleeding is extensive.
 
Although it is tempting to remove a blood clot during endoscopy, care should be exercised to avoid rupture of any underlying pseudoaneurysm with consequent torrential bleeding. Endoscopic biopsy of tissue around the oesophageal stent can also lead to pseudoaneurysm rupture as reported in an early case report by Kohl et al.1
 
Computed tomography is often useful to show the site of bleeding and corresponding anatomical relationship. Nonetheless a negative imaging may provide false reassurance. The pseudoaneurysm may be small because of impingement by the pointed oesophageal stent struts. This can be missed if the slice thickness of scan is not thin enough. Three-dimensional reconstruction images may provide more information. An on-table angiogram should be considered when the diagnosis is in doubt.
 
Fistulation of the carotid artery by a metallic oesophageal stent is rare and was first reported in 2001.1 Four previously reported cases were found in the literature.1 2 3 4 Among these cases, three adult patients had complications of previous treatments for carcinoma in the head and neck region, where two had oesophageal stricture1 3 and one had a tracheoesophageal fistula2; another 4-year-old paediatric patient had an oesophageal stent inserted for anastomotic stricture following surgical repair of oesophageal atresia.4
 
In Kohl et al’s report,1 resection was performed with a bypass using homograft made from the ascending aorta to the carotid bifurcation. Asymptomatic blockage of the graft was found soon after the procedure. The patient died of rebleeding 2 months later. Ali et al2 used endovascular coiling of pseudoaneurysm and stenting with a self-expandable nitinol stent. The patient had a rebleed 2 weeks later that required placement of a covered vascular stent. Staged open ligation of the common carotid artery was performed as a definitive treatment.2
 
A complete endovascular approach has been reported more recently. One patient received stenting to control bleeding and a staged operation to sacrifice the common carotid artery by endovascular coiling, but the long-term outcome was not reported.3 The paediatric patient was successfully treated with repeated coiling of the pseudoaneurysm and stenting with a bare-metal stent. He remained asymptomatic at a follow-up 1 year later.4
 
Endovascular treatment acted as a bridge to definitive management if quick open access is difficult due to anatomical constraints, as in our patient. Balloon occlusion test and cerebral perfusion scan can confirm adequate collateral supply before carrying out a second-stage operation to sacrifice the common carotid artery.2 3
 
The two major concerns with this temporising treatment are the risks of rebleeding and endograft infection. Definitive management should include surgical separation of the fistula. The oesophageal defect can be repaired primarily with or without reinforcement using diaphragm, intercostal muscle, serratus muscle, or omentum. Oesophagectomy or diversion are the other options if primary repair is not possible.
 
The diseased artery can be too friable for primary repair. Open ligation and endovascular coiling of the proximal carotid artery can be considered to prevent rebleeding provided an adequate collateral supply to the brain is confirmed.2 3 Revascularisation can be performed if required using bypass grafts from the aorta or subclavian artery. Operative risks include stroke, graft thrombosis and graft infection, especially when the surgical field is contaminated.
 
Similar fistulation between an aberrant right subclavian artery and oesophagus has been reported following oesophageal stent placement due to the anatomical relationship. Experience shows that most cases required immediate open surgery followed by tamponade using a hydrostatic dilator or Sengstaken–Blakemore tube. Surgery can be performed via a median sternotomy, thoracotomy or a manubrial resection. In patients with endovascular stenting as a temporising measure, the stent should be removed at the time of surgery to prevent oesophageal pressure necrosis due to a ‘sandwich effect’ with the oesophageal stent.5
 
For patients in whom definitive treatment is not possible, removal of an oesophageal stent can promote fistula healing. Proximal extension of a covered oesophageal stent may also minimise contamination from the aerodigestive tract. Long-term prophylactic antibiotics should be given but efficacy is not guaranteed. Alternatively, sacrificing unilateral carotid artery via an endovascular technique such as coils or plugs may prevent rebleeding. There is nonetheless no long-term evidence to support this technique.
 
Author contributions
All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided written informed consent for all treatment and procedures and for publication of this case report.
 
References
1. Kohl O, Rauber K, Doppl W. Perforation of an esophageal stent into the common carotid artery. Gastrointest Endosc 2001;53:374-8. Crossref
2. Ali AT, Kokoska MS, Erdem E, Eidt JF. Esophageal stent erosion into the common carotid artery. Vasc Endovascular Surg 2007;41:80-2. Crossref
3. Yadam S, Rali P, Balaan M, Lega M. A case of carotid-esophageal fistula masquerading as an upper gastrointestinal bleed. Am J Respir Crit Care Med 2016;194:e2-3. Crossref
4. Fachin CG, Demartini Z Jr, Pinto AS, et al. Carotidesophageal fistula treated by endovascular approach. Vasc Endovascular Surg 2021;55:419-21. Crossref
5. Merlo A, Farber M, Ohana E, Pascarella L, Crowner J, Long J. Aberrant right subclavian artery to esophageal fistula: a rare case and its management. Ann Thorac Surg 2020;110:e85-6. Crossref

Multisystemic smooth muscle dysfunction syndrome: the first local case report

Hong Kong Med J 2024 Feb;30(1):63–5 | Epub 8 Feb 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Multisystemic smooth muscle dysfunction syndrome: the first local case report
CH Ng, MB, ChB, MRCPCH; Grace PK Chiang, MSc, FHKAM (Paediatrics); KW Tsui, MRCP, FHKAM (Paediatrics)
Department of Paediatrics and Adolescent Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong SAR, China
 
Corresponding author: Dr CH Ng (nch234@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentation
In February 2020, a 7-year-old girl was brought to our institution. She had been experiencing dysphasia, dysphagia, and weakness in all four limbs for the past 5 days. She had no recent trauma, febrile illness or seizure. She had normal systolic blood pressure but diastolic pressure was persistently low for her age at 35 to 40 mm Hg. She had a Glasgow Coma Scale score of 11 (E4V1M6) with expressive aphasia. Pupils were equal but dilated at 5 mm and cranial nerves were grossly intact. The muscle strength of right lower limb power was the weakest, with a Medical Research Council (MRC) grade of 3, while others were at grade 4. She had brisk jerks over the lower limbs. Her medical history included premature birth at 34 weeks of gestation and surgical repair of a patent ductus arteriosus at 1 month of age. She also had recurrent urinary tract infections with megacystic bladder, managed since early infancy with intermittent bladder catheterisation. Magnetic resonance imaging of the brain was performed at the age of 5 years due to chronic headache and showed a large area of right frontal encephalomalacia that may have been due to a previous unknown insult.
 
Blood tests including complete blood count, electrolytes, inflammatory markers, lactate, ammonia, dried blood spot test, homocysteine, and plasma amino acids were unremarkable. Clotting profile, protein C, protein S and antithrombin III, and antinuclear antibodies levels were normal. Magnetic resonance imaging of the brain revealed acute ischaemic stroke with diffusion restriction in the left superior frontal, precentral, cingulate cortices, and corona radiata. Magnetic resonance angiography showed the anterior cerebral artery and middle cerebral artery were replaced by pruned cerebral arteries with straightened appearance and multifocal stenosis (Fig 1). Transthoracic echocardiogram showed a dilated aortic root of 23 mm with mild aortic regurgitation. Magnetic resonance aortogram showed comparable measurement with no aortic aneurysm or dissection (Fig 2).
 

Figure 1. (a) Magnetic resonance angiogram of the brain showing bilateral ectasia of internal carotid arteries from cavernous to clinoidal segments (arrow) and stenosis of the carotid terminus [arrowhead]. (b) The course of intracranial arteries is abnormally straight. The circle of Willis appears absent (arrows)
 

Figure 2. Magnetic resonance aortogram showing dilated aortic root (arrow) and prominent ascending aorta
 
To account for all clinical manifestations of the patient, a rare condition, multisystemic smooth muscle dysfunction syndrome (MSMDS), was suspected. Genetic analysis confirmed the diagnosis with a de novo heterozygous mutation of ACTA2 c.536G>A (Arg179His). No similar mutation was identified in her parents or younger sister.
 
Our patient was managed conservatively and prescribed oral aspirin. There have been five further episodes of ischaemic stroke or transient ischaemic attack to date. Developmental assessments revealed mild-grade intellectual disability with regression of gross and fine motor skills. During the latest follow-up, she could walk unaided and manage oral feeding. Physical examination showed grossly full proximal power. The right-hand flexors were weak (Medical Research Council grading of 4/5) and right lower limb was spastic. The patient is being followed by a multidisciplinary team comprised of a neurologist, cardiothoracic surgeon, neurosurgeon, and ophthalmologist.
 
Discussion
To the best of our best knowledge, this is the first identified case of MSMDS in Hong Kong. The ACTA2 gene encodes the thin filaments alpha-actin of the contractile element of smooth muscle. In 2010, Milewicz et al1 reported the first case series of patients with de novo missense mutation in the ACTA2 gene. Arg179His is the most severe form of this vascular disease spectrum. The three cardinal clinical presentations are congenital mydriasis, patent ductus arteriosus/aortopulmonary window, and white matter lesions with cerebrovascular disease.
 
Less common mutation loci, including Arg179Cys, Arg179Leu and Arg179Ser, have been reported to cause MSMDS.2
 
Neurological aspect
Recurrent ischaemic stroke is the major debilitating manifestation in MSMDS patients. Up to 95% of these patients have periventricular white matter hyperintensities evident on magnetic resonance imaging, signifying ischaemic insult in these watershed areas of blood supply. The vasculopathies were once considered a variant of moyamoya disease. Nonetheless MSMDS has some unique features, namely dilatation from the cavernous to the clinoid segments of the internal carotid arteries, stenosis and occlusive disease of the distal intracranial circulation, and an abnormally straight course of intracranial arteries. Stenosis of major cerebral arteries arises as a result of significant intimal thickening and markedly increased collagen and smooth muscle cells in the medial layers of these vessels.3
 
Neurosurgical management similar to that applied in moyamoya disease has been extrapolated to patients with MSMDS and includes direct superior temporal artery to anterior cerebral artery revascularisation and indirect revascularisation such as encephaloduroarteriosynangiosis. Nonetheless patients with various ACTA2 mutations respond less well to these operations. Almost half of affected patients who have undergone neurosurgical revascularisation continue to have major stroke episodes.4 After a case conference with neurosurgeons, anaesthesiologists, neurologists and the parents of our patient, we concluded that as surgery carried an exceedingly high risk with doubtful benefit, revascularisation was not considered.
 
Cardiovascular aspect
All reported cases of MSMDS have had a patent ductus arteriosus or aortopulmonary window with most requiring surgical ligation. Patent ductus arteriosus with diameter up to 20 mm in a neonate with MSMDS has also been reported.
 
Regalado et al2 reported that among the various ACTA2 mutations, Arg179His carries the highest risk of serious aortic events. By the age of 25 years, the cumulative risk of either elective aortic aneurysm repair or dissection is 100%.5 The group also suggested that elective surgical repair be considered when the aortic diameter reaches 4.5 cm.5 The benefit of drug therapy such as beta-blockers or angiotensin receptor blockers is unknown. It was not appropriate to prescribe either drug for our patient since further lowering of blood pressure would aggravate cerebral hypoperfusion leading to more stroke episodes.3
 
Apart from aortopathy, around half of MSMDS patients have peripheral arterial dilation involving the proximal internal carotid artery, common carotid brachiocephalic, subclavian, axillary and external/internal iliac arteries. This might also explain the low diastolic pressure.
 
Other systems
All reported cases of MSMDS have had pupillary abnormalities, mostly fixed or nonreactive pupils. Iris hypoplasia or aniridia has also been reported. Pulmonary complications, though not yet evident in our case, are also common. Pulmonary arterial hypertension may present in early infancy and necessitate mechanical ventilation, vasodilator drugs or even lung transplantation. Asthma and chronic lung disease have also been reported.
 
About half of MSMDS patients have hypotonic bladders. Recurrent urinary tract infections and hydronephrosis, as in our case, have also been frequently identified. One-third of patients have gastrointestinal problems such as gut malrotation, gastroesophageal reflux disease or constipation.2
 
In conclusion, MSMDS can affect multiple systems with life-threatening complications. Patients with congenital mydriasis, patent ductus arteriosus and recurrent stroke may raise a clinician’s suspicion of this rare condition and prompt early genetic investigations.
 
Author contributions
Concept or design: CH Ng.
Acquisition of data: CH Ng.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided informed consent for all treatments and procedures, and consent for publication.
 
References
1. Milewicz DM, Østergaard JR, Ala-Kokko LM, et al. De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A 2010;152A:2437-43. Crossref
2. Regalado ES, Mellor-Crummey L, De Backer J, et al. Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations. Genet Med 2018;20:1206-15. Crossref
3. Georgescu MM, Pinho M da C, Richardson TE, et al. The defining pathology of the new clinical and histopathologic entity ACTA2-related cerebrovascular disease. Acta Neuropathol Commun 2015;3:81. Crossref
4. Cuoco JA, Busch CM, Klein BJ, et al. ACTA2 cerebral arteriopathy: not just a puff of smoke. Cerebrovasc Dis 2018;46:159-69. Crossref
5. Regalado ES, Guo DC, Prakash S, et al. Aortic disease presentation and outcome associated with ACTA2 mutations. Circ Cardiovasc Genet 2015;8:457-64. Crossref

Primary penile tuberculosis masquerading as penile cancer: a case report

Hong Kong Med J 2023 Dec;29(6):554–5 | Epub 2 Nov 2023
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Primary penile tuberculosis masquerading as penile cancer: a case report
Ankitkumar Sharma, MS, DrNB (Urology); Deepak Velmurugan, MB, BS; Kuppurajan Narayanasamy, MS, FRCS (Urology)
Department of Urology, Kovai Medical Center and Hospital, Coimbatore, India
 
Corresponding author: Dr Ankitkumar Sharma (dr.ankitkumarsharma@gmail.com)
 
 Full paper in PDF
 
 
Case presentation
A 53-year-old man from northwest Tamil Nadu, India presented to our institution in January 2021 with a 3-month history of new-onset phimosis with swelling of the glans and an ulcer and penile discharge. The lesion presented initially with seropurulent discharge from the preputial sac. The patient later noticed some induration over the dorsal aspect that progressed further to an ulcer with frank purulent discharge. He had no family history of tuberculosis (TB) and no venereal disease or significant past surgical intervention. He had type 2 diabetes mellitus controlled by regular medication. His spouse had no significant history of pelvic inflammatory disease or secondary infertility and no present complaint of vaginal discharge, lower abdominal pain or productive cough.
 
On examination, the patient was of average built and nourishment. Vital signs were stable and examination of the respiratory, cardiovascular and gastrointestinal systems was unremarkable. Local examination of the external genitalia revealed staining of garments, phimosis, and an ulcer of 1×1 cm in size over the dorsal aspect of the penis with foul smelling purulent discharge near the corona. The glans palpable through the prepuce was hard in consistency and non-tender. The penile shaft was indurated up to the base and non-tender. There was no significant inguinal lymphadenopathy. Testes, spermatic cord and scrotum were clinically normal.
 
Blood investigations revealed haemoglobin level of 13.1 g/dL, white blood cell count of 6900/mm3, neutrophil level of 60%, platelet count of 234 000/μL, and glycated haemoglobin level of 7.8%; serology showed that human immunodeficiency virus, hepatitis B surface antigen and syphilis were non-reactive. Ultrasound of bilateral groin revealed a few inguinal nodes bilaterally, with the largest on the right measuring 8.7 mm. All nodes showed preserved fatty hilum and normal vascularity.
 
With the clinical diagnosis of localised carcinoma penis in mind, the patient was counselled about the need for intervention in the form of penile biopsy followed by total amputation of the penis with perineal urethrostomy. Under spinal anaesthesia, a dorsal slit was made in the penis that revealed penile oedema with purulent discharge from the preputial edge, multiple small granulomas and a hard and purulent cover over the glans. The glans penis was partially necrosed but the meatus was preserved. On extension of the dorsal slit to the base, the shaft was found to be covered in pus and slough with a hard consistency of the corpora cavernosa. Penile biopsy was taken from the glans and shaft. The slit cut surface was approximated at the base and haemostatic sutures placed over the glans to let the wound drain. A 16-Fr catheter was passed. Postoperatively, the patient was started on 4.5-g piperacillin sodium and tazobactam sodium via intravenous route three times a day. His postoperative course was uneventful with the wound showing purulent discharge, managed with twice daily saline dressings. The possibility of infectious origin of the disease was discussed with the patient.
 
After discussion with the pathologist, a provisional report was obtained of granulomatous inflammation with a few areas of necrosis. The need for culture and sensitivity was discussed with the patient, but due to financial constraints the patient was unwilling to proceed. He was initiated on anti-tubercular therapy as per regional antimicrobial policy. The final histopathology confirmed necrotising and granulomatous inflammation, with no acid-fast bacilli noted.
 
The patient and his partner were screened for pulmonary and genitourinary TB after the final histopathology report. The patient was discharged on postoperative day 9 with instructions to continue ATT for 6 months. He was advised to attend a local clinic for dressing changes every week until the wound had healed. The wound showed signs of healing on follow-up (Fig 1). After 6 weeks there were signs of build-up of slough. At 8 weeks, after completion of the intensive phase, the patient was referred for local surgical debridement and wound closure due to build-up of slough over the wound surface. He completed the course of ATT and the wound healed well (Fig 2). He has since developed erectile dysfunction, probably owing to secondary fibrosis of the corpora cavernosa. He does not desire treatment at this time.
 

Figure 1. Postoperative image of the patient at 2 weeks following dorsal slit and biopsy showing sloughed tissue extending to the base of penis
 

Figure 2. Intraoperative image of the patient at 8 weeks showing healthy granulation tissue following mobilisation of skin flaps of the penis
 
Discussion
Genitourinary TB is the most common form of extrapulmonary TB, but penile presentation is one of the least common forms of genitourinary TB (<1%).1 The epididymis (42%) followed by seminal vesicle (23%), prostate (21%), testis (15%) and vas deferens (12%) are common sites of presentation.2 In its primary form, local spread of bacilli from clothing, ejaculation, endometrial secretions, circumcision, and intravesical Bacillus Calmette–Guérin has been reported.2 The secondary form arises due to the subsequent complication of lung TB or TB in other parts of the urogenital tract, extending through the urethra or via a haematogenous route.
 
Tuberculosis of penis may affect the skin, glans penis or cavernous bodies. It can mimic penile carcinoma in presentation, much like our patient. Tuberculosis affecting the glans penis can present as tuberculous chancre, papulo-necrotic tuberculoid, TB cutis orificialis or tuberculous gumma. In most cases, the lesion takes the form of an ulcer that is difficult to differentiate from a malignant tumour. The lesion can be extensive, with involvement of the urethra and corpus cavernosum. Since young adults are affected, their partner should always be evaluated for genital TB.3 Although there are several tests for diagnosis of TB, biopsy remains confirmatory. Surgical management may be required in doubtful cases in spite of successful treatment with ATT. Organ sparing surgery coupled with ATT should be the goal of treatment.4
 
Our experience highlights the similarities in presentation of penile carcinoma and primary penile TB, further cementing the need for a dorsal slit prior to definitive procedure. A high index of suspicion should be maintained considering the endemic status of TB in South-East Asian countries. Biopsy should always be performed in doubtful cases.
 
Author contributions
Concept or design: A Sharma.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: A Sharma.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient for publishing of data relevant to the case report.
 
References
1. Nimisha E, Gupta G. Penile lupus vulgaris: a rare presentation of primary cutaneous tuberculosis. Int J STD AIDS 2014;25:969-70. Crossref
2. Amir-Zargar MA, Yavangi M, Ja’fari M, Mohseni MJ. Primary tuberculosis of glans penis: a case report. Urol J 2004;1:278-9.
3. Gangalakshmi C, Sankarmahalingam. Tuberculosis of glans penis—a rare presentation. J Clin Diagn Res 2016;10:PD05-6. Crossref
4. Rajeev TP, Pranab KR, Phukan PK, Baruna SK, Das Roop R. Tuberculosis of penis mimicking an advanced penile cancer—a case report. Int J Sci Res 2018;7:16-7.

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