Mystery case: jaw swelling and pain

Can you solve the mystery of a girl with unexplained episodes of jaw swelling and pain?  In this series, I will present the case of a patient I recently saw in clinic.  I will provide details of her history, physical exam, and medical tests.   Your job is to think like a doctor and answer the two questions below.   Continue reading Mystery case: jaw swelling and pain

A Doctor’s Prescription for Social Media – Part 2

This is the second post in the series “A doctor’s prescription for social media.”  The first post can be found here.

As an experiment,  I immersed myself in social media for the past three months.   Within this short period of time, I reaped tangible benefits.  In addition, social media has changed the way that I think about and practice medicine. Continue reading A Doctor’s Prescription for Social Media – Part 2

Horror autotoxicus: A story about self, non-self, and lupus

This is a guest post written by Dr. Christine Konya, a fellow in Rheumatology at Beth Israel Deaconess Medical Center.  She studies T cells in lupus.

Anyone interested in rheumatology or immunology will stumble on the findings by Paul Ehrlich, a scientist who helped to establish the field of immunology 100 years ago.  He received the Nobel Prize in 1908 for his work.  He is known for creating the “side-chain theory” of cells. He proposed that cells, when in danger, are able to express a variety of “side-chains” on their surfaces (now called “receptors”), which bind pathogens.  He further noted that when these “side-chains” break off, they work as “magic bullets” (now called “antibodies”) which circulate through the body and bind toxins.  Wasn’t he right?  He was also the first to think about autoimmunity.  He also discovered arsphenamie (Salvarsan), a compound to treat syphilis.   

“The organism possesses certain means, of which the immunity reaction is prevented from acting against the organism’s own elements and so giving rise to auto toxins … so that one might be justified in speaking of a ‘horror autotoxicus’ of the organism. These contrivances are naturally of the highest importance for the existence of the individual.” –Paul Ehrlich [1].

With “horror autotoxicus,” Dr. Ehrlich described the body’s fear of self-destruction. This is why our immune system has several control mechanisms to kill self-reactive T and B cells by inducing apoptosis. However, despite these complex mechanisms, autoimmunity does develop. Tolerance can be broken, and failure of these control mechanisms can lead to disease. One of the most dramatic manifestations of autoimmunity is seen in systemic lupus erythematosus.

The chief of our rheumatology division recently sent me an interesting article from Annals of Internal Medicine, published in 1952.  The article describes five young women, seen at the Cleveland Clinic in the 1940s, in whom false positive serologic test for syphilis was observed, without any signs of infection. After several years, these patients developed lupus.

“A 25 year old woman who was first seen at the Cleveland Clinic July 6, 1943, because of a history of positive serologic test for syphilis since 1941… from 1942 until 1943 she received 14 injections of bismuth and 27 injections of neoarsphenamine…General health remained good until 1946, when the patient developed a persistent cough. A roentgenogram of the chest was interpreted as chronic bronchitis. Wassermann reaction was 2 plus. A persistently low hemoglobin was noted which did not respond to iron therapy. The patient became weaker, noticed fever and abdominal cramping and developed icterus…Urine analysis revealed 3 plus albuminuria and microscopic hematuria. She was discharged and died at home one month later with pericarditis and pleural effusion.” [2]

At that time, testing for syphilis was performed with the “Wassermann test,” an older version of the VDRL. Patients with syphilis develop an antibody called reagin [3]. Reagin binds cardiolipin, a phospholipid found on the inner mitochondrial membrane of cells. Similarly, lupus patients can also develop anticadiolipin antibodies, and as a result, many were misdiagnosed.

Despite lingering evidence, the link between the false-positive syphilis test, the presence of anticardiolipin antibodies, and their correlation with lupus was not described until the 1980s, when Graham Hughes published his research on anticardiolipin antibodies and correlated them with increased incidence of thrombosis.  We now know that the anticardiolipin antibodies in lupus are similar, but not identical, to the ones seen in syphilis. They can be easily distinguished with a modern ELISA test.

The five women described in the article had a severe form of lupus and antiphospholipid syndrome, but were misdiagnosed as having syphilis. In these women, the false-positive syphilis testing was found when they attempted to donate blood or with routine blood testing prior to marriage.  I cannot imagine the impact that this test must have had on their lives. One of the women postponed her wedding due to the positive test and became severely depressed.

Fortunately, our knowledge has progressed, and our ability to diagnose and treat lupus has significantly improved.  We now realize that autoantibodies in autoimmune diseases, such as the anticardiolipin antibodies described above, are formed years before the onset of clinical symptoms.

My thoughts drifted back to Paul Ehrlich, and I ask myself what he would say about our current understanding of immunology, lupus, and autoimmunity, all of which is based on his visions.  What would he think about monoclonal antibodies, our “magic bullets” which we use for the treatment of many diseases?

I am certain that he would be very content with our advances in diagnosis and treatment of these diseases. For the future, I found this quote inspiring and worth aiming for:

“I see a world where no one ever dies from an adverse drug reaction; where physicians have an entire range of medicines to choose from to treat a deadly disease; where medications target tumors like smart bombs and leave surrounding tissues unharmed; where genetic susceptibility to disease can be determined in childhood, and possibly even prevented” Tim Downs, in his book Chop Shop.

 

Christine Konya, MD
Fellow in Rheumatology
Beth Israel Deaconess Medical Center
Follow me on Twitter @RheumatologyMD

 

 

References:

1.    The Collected Papers of Paul Ehrlich. Yale J Biol Med. Jun 1957; 29(6): 628. PMCID: PMC2603738.

2.    Systemic Lupus Erythematosus preceded by false-positive serologic tests for syphilis: Presentation of five cases. John R. Haserick and Roland Long, Ann Intern Med. 1952;37(3):559-565. doi:10.7326/0003-4819-37-3-559

3.  The 100th anniversary of Wassermann-Neisser-Bruck reaction. Bialynicki-Birula.  Clin Dermatol. 2008 Jan-Feb;26(1):79-88. doi: 10.1016/j.clindermatol.2007.09.020.

 

 

A doctor’s prescription for social media – Part 1

This is the first post in the series “A doctor’s prescription for social media.”  The second post can be found here.

As an experiment,  I immersed myself in social media for the past three months.  I started this blog, joined Twitter, LinkedIn, Google+, bought a domain name, and posted on Facebook for the first time in years.  Even within this short period of time, I reaped tangible benefits: I interacted with top physicians from across the world, kept up with the  medical literature, participated in discussions with patients about how how rheumatic diseases affect their lives, joined webinars about improving the patient experience, and provided educational information to physicians and patients about autoinflammatory diseases, my clinical interest.  Social media has changed the way that I think about and practice medicine, and it’s only been a few months. Continue reading A doctor’s prescription for social media – Part 1

Causa morbis ignota: A History of Lupus

This is a guest post written by Dr. Christine Konya, a fellow in Rheumatology at Beth Israel Deaconess Medical Center.  She studies T cells in lupus.

“We cannot say here causa mortis ignota [cause of death is unknown] but I should say causa morbis ignota [cause of the disease is unknown].” [1]

Dr. Cabot a physician at Massachusetts General Hospital was quoted as saying these words in an article published by the Boston Medical and Surgical Journal in May 1924. Today, this journal is known as the New England Journal of Medicine, officially renamed in 1928.  Dr Cabot was referring to a patient that likely had systemic lupus erythematosus. Back in those days, the disease was treated by dermatologists given the characteristic skin findings. The systemic features of lupus were not fully understood.  At that time, the disease was known as “disseminated lupus erythematosus,” considered to be associated to an infection such as tuberculosis, hence the word ”disseminated.”

In the same journal article, the confusion between TB and the new, partially described “disseminated” form of lupus erythematosus is apparent:

“-Dr. Means: What kind of skin tuberculosis did the skin people think this was?
-An Interne: Disseminated lupus erythematosus.
-Dr. Means: I thought lupus erythematosus was not a tuberculous disease at all.
-An Interne: It is thought not, but the disseminated form is.”

The idea of autoimmunity, diseases in which self-tolerance is broken, was completely unknown at that time, and the field of immunology barely existent.

Over the years, the systemic form of “lupus erythematosus” became evident. In an article published April 1934 by the New England Journal of Medicine, the disseminated form was described as the following:

“The following symptoms of acknowledged import occurred: erythematous cutaneous lesions, rheumatoid pains, hemorrhagic tendencies, high fever, and leucopenia. Roxburgh says that these fatal cases start from a chronic, localized type, that they are more frequent in women, and that they usually occur between the ages of 20 and 30 years. The presence of arthritis, arthralgia, muscular pains, albuminuria, a purpuric eruption, and a high fever are of bad prognostic significance and suggest the onset of a fatal ending. Death occurs in from one to four months after the beginning of these symptoms.” [2]

A few years later, in November 1938, a Boston dermatologist by the name of Dr. Tolman  published the following description about lupus erythematosus in the same journal.  A description of lupus which remains relevant almost 100 years later:

“It is generally accepted that there are four main clinical types of lupus erythematosus: the chronic discoid or fixed, the chronic disseminate, the subacute disseminate and the acute disseminate. The present paper deals exclusively with the discoid or fixed type. This form occurs chiefly on the face (where it characteristically attacks the bridge of the nose and the flush areas of the cheeks, the so-called butterfly outline), ears, mucous membranes and scalp. The early lesion is an erythematous and slightly elevated macule The course of the disease is chronic, afebrile and benign, in contrast with the disseminate forms, which are acute in onset, and are associated with fever and a multitude of pathologic findings, and which are only too frequently fatal.” [3]

Slowly, the field of immunology evolved, but the diagnosis of lupus erythematosus was still challenging to make in the absence of serologic markers. It was not until the late 1950’s when anti-nuclear antibody (ANA) was detected in patients with lupus, and it gradually became part of its diagnosis.

In regards to treatment, not much was available until the discovery of cortisone, for which Reichtein, Kendall, and Hench were awarded the Nobel Prize in 1950. Treatment with antimalarials began in 1951 with quinacrine. Both drugs significantly increased quality of life and life expectancy. These medicines are still the backbone of lupus therapy to this day, although other drugs are also being used to manage disease activity.

We now have a better understanding of lupus and autoimmunity in general.  We know that an imbalanced immune system with malfunctioning immune cells are the cause of tissue inflammation. It is likely that the disease we call systemic lupus erythematosus is actually a group of related disorders, not a single disease entity. However, we are still working to decipher how and why immune cells lose tolerance to self-antigen, and how the intracellular signaling cascades lead to an abnormal inflammatory response.

Treatment options for most rheumatic diseases have dramatically increased over the last two decades, also becoming more effective with the development of targeted therapy with biologics. In contrast, treatment for lupus has not yet entered its renaissance. Biologics did not meet our expectations in controlling disease, but research is rapidly evolving. The goal remains to develop personalized and target treatment options to control and eventually cure disease.

I still think that Dr. Cabot’s words from 1924 still hold true today: “Causa morbis ignota,” the cause of the disease is unknown.

 

Christine Konya, MD
Fellow in Rheumatology
Beth Israel Deaconess Medical Center
Follow me on Twitter @RheumatologyMD

 

Works Cited:
1.  Case Records of the Massachusetts General Hospital: Case 10223.  Boston Med Surg J 1924; 190:945-950.
2.  Towle and Grund.  Progress in Dermatology.  N Engl J Med 1934; 210:756-765.
3.  Maurice M. Tolman, M.D.  Lupus Erythematosus Discoides — Its Present Status with Regard to Etiology and Treatment. N Engl J Med 1938; 219:688-697.

Uncovering the mysteries of autoinflammatory diseases and other rheumatic illnesses.

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