The "first hit" in the hypothesis is proposed to be genetic susceptibility and surrounding environmental factors and the "second hit" would be the introduction of the antigen into the respiratory system which causes the exaggerated immune response. Diagnosis
The diagnosis is made through clinical judgement using a combination of findings because there does not exist a single, universal diagnostic criteria for the disease. The diagnosis is most commonly ascertained first with a detailed exposure history followed by a battery of clinical tests including: imaging, histopathology, pulmonary function testing, serology, bronchoscopy, and more. In 2020, official guidelines were published by American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax which provides a systematic approach to the diagnosis of HP that relies on high-resolution computed tomography. Exposure History
A detailed occupational, home and environmental exposure history is the first step in diagnosis. Unfortunately, only 60% of inciting antigens are identified in exposure assessment. Re-exposure to the antigen can help aid in diagnosis. Standardized questionnaires have been created to help in obtaining an exposure history although no official questionnaire has been purported. It has been recommended that the questionnaire administered should be relevant to the region in which the exposure has potentially occurred.Detailed exposure assessments are warranted in the cause of damp indoor environments which have the potential to propagate mold throughout the dwelling. The decision to enlist an industrial hygienist should be made based on the answers to evidence based questions during the environmental assessment.
Subacute combined degeneration of spinal cord, also known as myelosis funiculus, or funicular myelosis, also Lichtheims disease, and Putnam-Dana syndrome, refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency (most common), vitamin E deficiency, and copper deficiency. It is usually associated with pernicious anemia. Signs and symptoms
The onset is gradual and uniform. The pathological findings of subacute combined degeneration consist of patchy losses of myelin in the dorsal and lateral columns. Patients present with weakness of the legs, arms, and trunk, and tingling and numbness that progressively worsens. Vision changes and change of mental state may also be present. Bilateral spastic paresis may develop and pressure, vibration and touch sense are diminished. A positive Babinski sign may be seen. Prolonged deficiency of vitamin B12 leads to irreversible nervous system damage. HIV-associated vacuolar myelopathy can present with a similar pattern of dorsal column and corticospinal tract demyelination.It has been thought that if someone is deficient in vitamin B12 and folic acid, the vitamin B12 deficiency must be treated first. However, the basis for this has been challenged, although due to ethical considerations it is no longer able to be tested if "neuropathy is made more
severe as a result of giving folic acid to vitamin B12-
deficient individuals".