People do not resort to alternative medicine because they are stupid or irrational, but because they are desperate and hopeless.

No amount of logic & education can convince a drowning man to stop paddling & flailing his limbs even though he knows that he can't swim and that his frantic motion is all in vain.

There are multiple criteria, but the most famous is the American College of Rheumatology (ACR) criteria. It contains 11 elements. The diagnosis of SLE is confirmed when 4 or more of the criteria have been met.

تبقى ملاحظة كلش مهمة:

ANA & anti-dsDNA are part of the routine investigation for SLE, but there are many caveats to be considered when interpreting them:

Since anti-dsDNA antibodies are part of ANA, the presence of anti-dsDNA antibodies in the absence of ANA is a rare phenomenon and may be due to laboratory error.

Which is why the ACR guideline states that you should send for ANA first, and if positive, send for the more specific anti-dsDNA. This has proven to limit diagnostic errors and is cost-effective.

Several laboratory techniques are commercially available to measure anti-dsDNA, like ELISA, Farr, and CLIFT. The latter two being more specific and thus less liable for false-positives.

For that reason, ELISA method may be used as an initial screening followed by the CLIFT for positive sample confirmation. In 2007, a Japanese group suggested performing a highly specific anti-dsDNA testing (as Farr or CLIFT), and if ELISA was used, a positive test result must be subsequently confirmed by the CLIFT method.

تبقى نقطة أخيرة:
الـ anti-dsDNA ممكن يكون عالي (هو والـ ANA) بعدّة أمراض غير الـ SLE. وبنفس الوقت، أكثر من دراسة شافت أنّ، مقارنةً بالدول الغربية، نسبة أعلى من سكان البلدان العربية ممكن يكون عدهم anti-dsDNA عالي وبنفس الوقت ما عدهم SLE. هالشي يجعل هالتحليل less specific than we thought.

Initial Western reports showed that the frequency of elevated levels of anti-DNA antibodies in conditions other than SLE to be low (less than 5% of the patients), and when they are present, are often in low titer and with low avidity. In 1995, a Saudi study showed that anti-dsDNA using ELISA could be positive in 35% of patients with rheumatological disorders, and 4% in normal patients. In Oman, it was found in 23% disease control, 16% in RA patients, and 3% in normal individuals. Therefore, why in Arab countries do we have such a high false-positive anti-dsDNA in the blood in comparison to Western society? This could be explained by the theory of “ultraviolet (UV) light-induced keratinocyte apoptosis.” The dsDNA antigen is available in the human skin and most of the Arab countries are subtropical and arid where the climate is >40°C. In patients predisposed to autoimmune diseases, exposure to ultraviolet light (UVA and UVB waves in the sunlight) will damage skin cells (keratinocytes) causing them to die (apoptotic). These cells are not cleared away efficiently, and result in the contents of the dying cells as DNA being released into the blood stream, causing inflammation, which may generate an immune response.

هاي دراسة سعودية فحصت 212 مريض عدهم الـ dsDNA +ve بس مع ذلك، نصهم فقط جان عدهم SLE.

اني ليش مدوخ روحي ومدوخكم بهاي التفاصيل؟
لأن شفت مريضة مشخصيها على أنها SLE وهي (بشهادة الطبيب اللي مشخصها) ما عدها غير 2 من أصل 11 من الـ ACR criteria اللي هي الـ immunological والـ arthritis، وحتى ذني مو أكيدات. بس الطبيب من شاف الـ anti-dsDNA +ve جزم بأنها مصابة بالمرض.

بالنسبة للـ immunological فهي عدها الـ anti-dsDNA +ve بنسبة مو عالية (low titer positive)، بس بنفس الوقت الـ  ANA مالتها ve- وهالشي يخليك تشك بأنّ النتائج بيها خطأ من المختبر.

أما الـ arthritis، فالمريضة تعاني ألم بمفاصل وعظام الإيد والرجل. لما تباوع على تاريخها الطبي رح تشوف عدها إنزلاق بالرقبة وبالفقرات القطنية ووياها رشة carpal tunnel syndrome وتاريخ سابق بالـ RA وبدايات DM. بالإضافة إلى أنّ عمرها يطلع بالخمسينات (هالشي يقلل إحتمالية الـ SLE ويزيد إحتمالية الـ osteoporosis). كل هاي المشاكل ممكن يساهمن بزيادة ألم المفاصل ويفسرن أعراضها بشكل أفضل وأبسط وأدق من فرضية الـ SLE اللي هي أصلًا ما عليها دليل clinical (والدليل الـ immunological مشكوك به) وملزّكيها تلزيك.

هاي بدون الأخذ بنظر الإعتبار أنّ علاج الـ SLE بحد ذاته مزعج ويتضمن immunosuppression، لهذا لا تشخص مريض بالمرض إلا وانت متأكد. هي مو نشلة وتنطيه بنادول أو ما تنطيه هو يطيب من وحده.

Damn, I was close...

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Also, this a great chance to talk about the limitations of lab tests and imaging modalities. I mentioned it earlier: the diagonsis of a disease is based on accurate history & exam. The investigations are confirmatory/elemenation tools. They were never meant to diagnose a disease without first relying on a proper history & exam (and subsequently, a good differential diagnosis).

A known case of thoracic aortic aneurysm

A suspected case of thoracic aortic aneurysm I found in the ER.

The patient choked on food and was admitted for shortness of breath. He had a chest x-ray done, and we found this incidentally.
Couldn't examine him properly though, because he was dyspneic :")

Update:
راحت لأطباء روماتو ثنين، وعادت التحاليل مرتين، مرة طلعت نفس النتيجة (anti-dsDNA +ve in low titer والـ ANA هالمرة +ve). والتحليل الثاني طلع -ve. وبعدها ما عدها علامات سريرية للمرض. بالنتيجة اعتبروا أنّ ما عدها SLE (الطبيبة الثانية نصحتها تاخذ الأدوية prophylactically and just in case) بس المريضة رفضت خوفًا من الأعراض الجانبية. ورح تعيد التحليل بعد 6 أشهر.

To make things even more complicated, SLE patients can have +ve serology two to one year prior to clinical manifestations. Which is why it's advicable to redo the tests a few months later (granted the lab is trustworthy).