Pulmonary Angiothrombotic Granulomatosis

A female patient aged over 40 years with chronic pain syndrome and multiple substance use (dependency syndrome) died unexpectedly 10 days after she had been admitted to hospital for pain medication optimization. A radiograph obtained before her death had shown interstitial pulmonary changes without functional impairment; however, further investigations failed to establish a definite diagnosis (Figure 1). Autopsy revealed disseminated changes in both lungs, resembling milliary tuberculosis. Histologically, these were found to be giant-cell granulomas, surrounding masses of intravascular amorphic foreign material (Figure 2). Focal residuals of past bleeding (hemosiderin) provided evidence of older and recent immune responses to birefringent crystalline and amorphous structures. Toxicology testing revealed a toxic oxycodone concentration in femoral venous blood (unknown duration/dosage of substance use). An explanation of these findings was found in rare case reports: Patients on opioid replacement therapy who dissolved their methadone tablets and then injected the solution developed pulmonary angiothrombotic granulomatosis in response to the introduction of cellulose and other excipients in tablets (e.g., binding agents) into the lungs. As a result, these patients can develop dyspnea and pulmonary hypertension which, in combination with a respiratory depression-inducing ingredient (in this case: oxycodone), can lead to a fatal outcome.

Figure 1

Radiograph showing hilar enlargement (arrows) and increased interstitial markings.

Figure 2

Histological specimen of the lung with evidence of partly birefringent (black asterisk), partly amorphous (red asterisk) foreign material in a medium-sized pulmonary vessel (red arrows). Van Gieson‘s stain used to stain connec tive tissue; in polarized light (magnification: bar = 200 µm).

Dr. rer. biol. hum. Julia Krüger,
Prof. Dr. med. Oliver Peschel, Prof. Dr. med. Andreas G. Nerlich,
Institut für Rechtsmedizin, Ludwig-Maximilians Universität München,

Conflict of interest: The authors declare no conflict of interest.

Translated from the original German by Ralf Thoene, MD.

Cite this as: Krüger J, Peschel O, Nerlich AG: Pulmonary angiothrombotic granulomatosis. Dtsch Arztebl Int 2025; 122: 392. DOI: 10.3238/arztebl.m2025.0064