Many diseases in patients with multimorbidity show interactions, which can be divided in random, causal, complicated of synergistic interactions. Diagnostic reasoning in general should be expanded with a goal assessment when single disease directed guidelines are not applicable to limit diagnostic burden and troubling incidental findings without added diagnostic value. Disease directed diagnostic guidelines are not well adapted to symptoms and complaints of patients with multimorbidity, which urges to first explain these based on progression of the multimorbidity, and only if necessary, expand this to diagnostic work-up for new diseases. Shared decision making on additional diagnostic investigations should anticipate and safeguard added therapeutic value of diagnostic results. New instruments such as causal loop diagrams, which clarify interactions between the individual diseases, may support this multimorbidity targeted diagnostic reasoning.

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