Estrogen;

Why Does My Young Female Patient Have Recurrent Spontaneous Pneumothoraces?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Causes of spontaneous pneumothorax are legion, including cigarette use, genetic predisposition, or most commonly subpleural bleb rupture. 1 However, in cases without an apparent cause, a young female patient with recurrent spontaneous pneumothorax should routinely be asked about the timing of the pneumothorax in relation to her menstrual periods.  If related, catamenial pneumothorax (CP)— also known as menses-associated pneumothorax—should also be considered.  

CP is commonly defined as 2 or more episodes of spontaneous pneumothoraces occurring within 72 hours of onset of menstruation. 2, 3 Classically, CP occurs in females between the ages of 30-40 years with a history of endometriosis and recurrent right-sided pneumothorax.

As for potential mechanisms to explain catamenial pneumothorax, several theories have been proposed, including the passage of air through the vagina and uterus during times of decreased cervical mucus production and peritoneal cavity into the pleural space via diaphragmatic fenestrations. 3 Another potential mechanism is the retrograde migration of endometrial tissue from the uterine lining via the right paracolic gutter into the pleural space through defects in the diaphragm. Endometrial necrosis following monthly cycles may then create air blebs and pneumothorax. 3,4 Although CP is the most common presentation of thoracic endometriosis, a diagnosis of endometriosis is not required for its diagnosis.3, 5

Initial evaluation of CP often includes chest X-ray, CT, or MRI which may show not only pneumothorax but also diaphragmatic nodules or fenestrations; CA-125 levels may also be elevated in CP due to endometriosis. 2,3,9  Endometriosis-related CP is diagnosed via video-assisted thoracoscopic surgery (VATS).  

Treatment includes surgical and medical options but, ultimately, the goal is to prevent recurrence which is more likely in CP compared to other pneumothoraces. 3, 6 Surgical approaches such as VATS, pleurodesis, and diaphragmatic plication or repair with mesh, may be considered but recurrence rates (8-40%) are common. 3,7 Treatment options also include hormone-suppression therapy resulting in atrophy of ectopic endometrial glands (eg, estrogen-progesterone oral contraceptives and gonadotropin-releasing-hormone [GNRH] agonists such as leuprolide). 2, 7

Bonus Pearl: Did you know that a condition called catamenial epilepsy also clusters around menstruation due to the diminished protective effect of progesterone against seizures?  10

Contributed by Mariam Krikorian, Medical Student (Lincoln Memorial University) Mercy Hospital-St. Louis

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References

  1. Sahn, Steven A., Heffer, John E. Spontaneous Pneumothorax. N Engl J Med. 2000;342:858-874. https://www-nejm-org.lmunet.idm.oclc.org/doi/10.1056/NEJM200003233421207?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
  2. Haga, T., Kumasaka, T., Kurihara, M, etal. Immunohistochemical Analysis of Thoracic Endometriosis. Path Intl, 2013;63(9);429-434. https://onlinelibrary.wiley.com/doi/10.1111/pin.12089.
  3. Visouli, A. N., Zarogoulidis, K., Kougioumtzi, I., etal. Catamenial Pneumothorax. J Thora Dis. 2014;6(4). https://jtd.amegroups.com/article/view/3205/html.
  4. Rousset-Jablonski, C., Alifano, M., Plu-Bureau, G., etal. A. Catamenial Pneumothorax and Endometriosis-Related Pneumothorax: Clinical Features and Risk Factors. Mol Hum Reprod. 2011;26(99);2322-2329. https://academic.oup.com/humrep/article/26/9/2322/720483.
  5. Korom, S., Canyurt, H., Missbach, A., etal. Catamenial Pneumothorax Revisited: Clinical Approach and Systematic Review of the Literature. J Thorac Cardiovasc Surgery. 2004;128(4);502-508. https://www.jtcvs.org/article/S0022-5223(04)00772-X/fulltext.
  6. Haga, T., Kurihara, M., Kataoka, H., etal. Clinical-Pathological Findings of Catamenial Pneumothorax: Comparison Between Recurrent Cases and Non-Recurrent Cases. Ann Thorac. 2014;202(6);202-206. https://www.jstage.jst.go.jp/article/atcs/20/3/20_oa.12.02227/_article.
  7. Leong, A. C., Coonar, A. S., Lang-Lazdunski, L. L. Catamenial Pneumothorax: Surgical Repair of the Diaphragm and Hormone Treatment. Ann R Coll Surg Engl. 2006;88(6). https://publishing.rcseng.ac.uk/doi/10.1308/003588406X130732.
  8. Marjański, T., Sowa, K., Czapla, A., etal. Catamenial Pneumothorax – A Review of the Literature. Polish Journal of Thoracic and Cardiovascular Surgery. 2016;13(2);117-121. https://www.termedia.pl/Catamenial-pneumothorax-a-review-of-the-literature,40,27920,0,1.html.
  9. Bagan, P., Le Pimpec Barthes, F., Assouad, J, etal. Catamenial Pneumothorax: Retrospective Study of Surgical Treatment. Ann Thorac. 2022;75(22);378-381. https://www.annalsthoracicsurgery.org/article/S0003-4975(02)04320-5/fulltext.
  10. Herzog, Andrew. Catamenial Epilepsy: Definition, Prevalence, Pathophysiology and Treatment. Elsevier Sci. 2008;17;151-159. https://pubmed-ncbi-nlm-nih-gov.lmunet.idm.oclc.org/18164632/.

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Why Does My Young Female Patient Have Recurrent Spontaneous Pneumothoraces?

Does Covid-19 affect males more than females?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

Although there is no clear gender pattern in terms of susceptibility to Covid-19, once infected, men have consistently been shown to have higher fatality rates when compared to women.1

In an earlier study involving over 1000 Covid-19 patients, males accounted for 58% of cases.2  However, a review of over 72,000 patients reported by the Chinese CDC found nearly equivalent male to female ratio (~1:1).3 Among Covid-19 patients who have died, male to female ratio has frequently been found to be between 1.5-3.8:1, depending on the reporting country.1  

In a case series from New York City, males accounted for 55% of Covid-19 patients not on invasive mechanical ventilation but 71% of those who required invasive mechanical ventilation.4 Chinese CDC reported case fatality rates of 2.8% for males and 1.7% for females.3 Higher case-fatality rates among males with 2 other coronavirus-related diseases, SARS and MERS, have also been reported.5

Potential explanations for more fatal outcomes among males with Covid-19 include more robust innate and humoral immune responses to infections among females.6 Immune suppressive activity of testosterone and potential immune enhancing effects of estrogens, such as increased expression of the anti-viral cytokine interferon (IFN)-gamma, have long been recognized.6 Life style differences between men and women such as higher prevalence of smoking in men are often mentioned as well.7 Interestingly, circulating ACE2, a receptor for SARS-CoV-2, has also been reported to be higher in men.8

Bonus pearl: Did you know that testosterone is associated with decreased production of pro-inflammatory cytokines such as IFN-gamma, TNF-alpha and may suppress immunoglobulin production?6

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 References

  1. Global Health 5050. Towards gender equality in global health. http://globalhealth5050.org/covid19/ , accessed April 27, 2020.
  2. Guan WJ, Ni AY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;Feb 28, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2002032
  3. Chinese CDC. Vital surveillances: the epidemiological charcteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)-China, 2020; 2:113-22. http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
  4. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med 2020, April 17. https://www.nejm.org/doi/full/10.1056/NEJMc2010419
  5. Channappanavar R, Fett C, Mack M, et al. Sex-based differences in susceptibility to SARS-CoV infection. J Immunol 2017;198:4046-4053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450662/#!po=3.84615
  6. Ysrraelit MC, Correale J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology 2018;156:9-22. https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13004
  7. Wenham C, Smith J, Morgan R. COVID-19: the gendered impacts of the outbreak. Lancet 2020:395:846-7. https://www.ncbi.nlm.nih.gov/pubmed/32151325
  8. Patel SK, Velkoska E, Burrell LM. Emerging markers in cardiovascular disease: Where does angiotensin-converting enzyme 2 fit in? Clin Exp Pharmacol Physiol 2013;40:551-9. https://www.ncbi.nlm.nih.gov/pubmed/23432153/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Does Covid-19 affect males more than females?

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

 

There are many causes of low serum haptoglobin besides hemolysis, including1-4:

  • Cirrhosis of the liver
  • Disseminated ovarian carcinomatosis
  • Pulmonary sarcoidosis
  • Elevated estrogen states
  • Repetitive physical exercise
  • Hemodilution
  • Blood transfusions
  • Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
  • Iron deficiency anemia
  • Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
  • Congenital causes

Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.

Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?

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References

 

  1. Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
  2. Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
  3. Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

Why does my patient with alcoholic liver disease have spider angiomas?

FA Manian MD, MPH, , , , Leave a comment

 

Spider angiomas (SAs), collections of small blood vessels radiating from a central, dilated arteriole that form near the surface of the skin, are  found in 10-15% of healthy adults and young children, as well as in a variety of conditions, including pregnancy, women taking oral contraceptive pills (OCPs),  thyrotoxicosis, and chronic liver disease1.  

Although the exact mechanism of the formation SAs has not been fully elucidated, several hypotheses have been offered:

  • Arteriolar vasodilation caused by estrogen excess due to impaired hepatic metabolism in cirrhosis; 2this is supported by the association of SAs also with other high-estrogen states, such as in pregnancy and OCPs.
  • Vasodilatory effects of substance P, a neuropeptide partially inactivated by the liver and elevated in patients with liver disease. 3 
  • Neovascularization promoted by vascular endothelial growth factor and basic fibroblast growth factor released by damaged hepatocytes. 4
  • Alcohol itself may contribute, as SAs are more commonly seen in individuals with alcoholic cirrhosis than in those with non-alcoholic causes of liver disease. 2

For unknown reasons, in adults spider angiomas most commonly occur in areas drained by the superior vena cava, namely the face, arms, neck, and chest.

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References

  1. Khasnis A, Gokula RM. Spider nevus. J Postgrad Med 2002;48:307.         
  2. Li CP, Lee FY, Hwang SJ, et al., Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol 1999;  34: 520-3.https://www.ncbi.nlm.nih.gov/pubmed/10423070
  3. Li CP, Lee FY, Hwang SJ, et al., Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis. Am J Gastroenterol 1999; 94: 502-7.https://www.ncbi.nlm.nih.gov/pubmed/10022654
  4. Li CP, Lee FY, Hwang SJ,  et al., Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol 2003; 9: 2832-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612064/ 

Contributed by Camille Mathey-Andrews, Medical Student, Harvard Medical School

 

Why does my patient with alcoholic liver disease have spider angiomas?