Difficult diseases refer to diseases where the diagnosis is not clear, or the treatment is difficult. If the diagnosis is unclear, there is no choice of treatment plan; if the treatment is difficult, the correctness of the diagnosis should be re-examined. Therefore, there is a close dialectical relationship between doubt and difficulty, so the two are often mentioned together. We found many difficult diseases related to rheumatism in the clinic. A patient with coronary artery disease combined with heart failure was once diagnosed with nodular polyarteritis (one of the rheumatic diseases) by a consultation with a rheumatologist after conventional anti-heart failure treatment was ineffective. Another patient with thrombocytopenia was treated with adrenocorticotropic hormone, but her platelets still did not improve and her clinical symptoms increased without decreasing. When asked about the medical history, this female patient had a history of multiple unexplained miscarriages, and was found to have strong positive anti-cardiolipin antibodies, diagnosed as antiphospholipid antibody syndrome, and the platelet count gradually increased after aspirin treatment. It shows that in clinical work, the thinking should be broad, and one should know the common and the change. When the treatment of common diseases is ineffective, the analysis from the perspective of rheumatism may have the meaning of “another village in the dark”. The following is a brief description of the common and difficult diseases related to rheumatism: Fever The causes of fever are many and complex, and unexplained fever is often related to rheumatism. Most rheumatic diseases have symptoms of fever, either high or low fever, or continuous fever or intermittent fever, or irregular fever. It is ineffective with antimicrobial agents, and blood cultures are negative. Common rheumatic diseases with fever such as rheumatic fever, systemic lupus erythematosus, polymyositis dermatomyositis, adult Steele’s disease, recurrent febrile nonsuppurative nodular lipofuscinosis, Kawasaki disease, nodular disease, Lyme disease, etc. Ophthalmology Ophthalmology is not limited to ophthalmology, and many ophthalmology diseases have to be considered for diagnosis and treatment from an internal medicine perspective or rheumatology perspective. Rheumatic diseases with ophthalmology are more common and can manifest as conjunctivitis, iritis, chorioretinitis, uveitis, retinitis, anterior chamber pus accumulation, optic neuropathy, etc. Common rheumatic diseases with ophthalmopathy such as ankylosing spondylitis, giant cell arteritis, recurrent polychondritis, deformational osteitis, nodular disease, Wegener’s granulomatosis, etc. Jaundice Jaundice is a common sign resulting from abnormal bilirubin metabolism and excretion in the body, manifested as yellowing of the eye sclera and the skin of the body, mostly associated with hepatobiliary pathology. Jaundice with an unclear primary cause should be ruled out for rheumatic disease. Common rheumatic diseases with jaundice such as: adult Steele’s disease, systemic lupus erythematosus, dry syndrome, mixed connective tissue disease, etc. Effusion There are many causes of pleural, abdominal, and pericardial cavity effusion. Clinically, it is often difficult to identify the primary cause of pleural, abdominal, and pericardial cavity effusion. Common rheumatic diseases with pleural, abdominal, and pericardial cavity effusions include: systemic lupus erythematosus, polymyositis, mixed connective tissue disease, leukoaraiosis, recurrent polychondritis, POEMS syndrome, and Whipple disease. Encephalopathy Encephalopathy related to rheumatism mostly manifests as abnormal behavior, indifferent expression, sudden frenzy or cerebrovascular accident. The diagnosis of rheumatic diseases with encephalopathy as the first symptom is more difficult. Common rheumatic diseases with encephalopathy include systemic lupus erythematosus, antiphospholipid antibody syndrome, systemic vasculitis, etc. Anemia Anemia refers to a decrease in blood red blood cells, hemoglobin, and red blood cell ratio. Symptoms such as dizziness and palpitations are often present. Common rheumatic diseases with anemia such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, systemic sclerosis, polymyositis dermatomyositis, polyarteritis nodosa, Wegener’s granulomatosis, recurrent polychondritis, and nodular disease. The appearance of the above-mentioned manifestations, difficult to explain with other diseases or invalidated by conventional treatment, should be considered to have rheumatic diseases, to promptly go to the rheumatology specialist, may have unexpected gains.