Loefflers syndrome historical perspective

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Wilhelm Löffler in 1961 (1887-1972), was a respected Swiss clinician scientist. Source. Nationaal Archief: https://www.nationaalarchief.nl/onderzoeken/fotocollectie/detail/a9d4bf64-d0b4-102d-bcf8-003048976d84urce:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

In 1932, Wilhelm Löffler drew attention to the disease in cases of eosinophilic pneumonia caused by the parasites such as Ascaris lumbricoides, Strongyloides stercoralis and the hookworms, such as Ancylostoma duodenale and Necator americanus. Although Löffler only described eosinophilic pneumonia in the context of infection, many authors give the term "Löffler's syndrome" to any form of acute onset pulmonary eosinophilia no matter what the underlying cause. If the cause is unknown, it is specified and called "simple pulmonary eosinophilia".

Historical perspective

• In 1909, H. French described three categories of eosinophilia in a clinical lecture later published in the Guy’s Hospital Gazette. The three categories he included were:(ref:French WH. Eosinophilia. Guy’s Hospital Gazette. 1909;23:533-537.)"Guy's Hospital Gazette - Google Books".

• Asthma
• Parasitic infections, such as “Anchylostomiasis, Bilharzia huematobia, Trichina spiralis, Hydatid disease; and to less extent with Taenia solium, Taania medio canellata, and Bothriocephalus latus; whilst it does not occur at all with Trichocephalus dispar, Oxyuris vermicularis, or Scabies; and Ascaris lumbricoides.”
• Skin diseases such as bullous dermatoses: “Pemphigus, Erythema bullosiim, Erythema iris, Dermatitis herpetiformis, and Herpes gestationis.”

• In 1922, Koino, a dedicated Japanese clinician scientist studied Ascaris on humans.

• He himself ingested 2000 mature eggs of human Ascaris, which produced symptoms of pneumonia, including fever, dyspnoea, productive cough, haemoptysis, and sputum containing larvae. Koino named it ‘Ascaris pneumonia’.
• He also made an experiment on his brother , he fed his younger brother 500 mature Ascaris eggs from the pig, and observed and episode of fever, dyspnoea, and productive cough without blood or sputum containing larvae. (ref:Koino, S. Experimental infection on the human body with ascarides. Japan Med. World, Tokyo, Japan, 1922, V. 2, pp.317-320) 317-320.)

• Then in 1932, Wilhelm Löffler drew attention to the disease in cases of eosinophilic pneumonia caused by the parasites such as Ascaris lumbricoides, Strongyloides stercoralis and the hookworms, such as Ancylostoma duodenale and Necator americanus. (ref:
  • Löffler W. Zur Differential-Diagnose der Lungenifiltrierungen. I. Frühfiltrate unter besonerer Berücksichtigung der Rückbildungszeiten. Beiträge zur Klinik der Tuberkulose. 1932;79(3-4):338–367.)
  • (Löffler W. Zur Differential-Diagnose der Lungenifiltrierungen. II. Über flüchtige Succedan-Infiltrate (mit Eosinophilie). Beiträge zur Klinik der Tuberkulose. 1932;79(3-4):368–382. [Löffler syndrome])
  • (Löffler W. Zur Differential-Diagnose der Lungeninfiltrierungen. III. Über Differential-Diagnose der Sekundärinfiltrierungen. Beiträge zur Klinik der Tuberkulose. 1932;79(5):566–576.)
  • (Löffler W. Flüchtige Lungeninfiltrate mit Eosinophilie. Klinische Wochenschrift. 1935;14(9):297–299)
  • (Loeffler, W. Die fluchtigen Lungeninfiltrate mit Eosinophile. Schweiz. med. Wchnschr. 1936; 66:1069.)

• In his first report, Löffler described four cases of transient (lasting 3-8 days) pulmonary infiltrates on chest X-ray, with very little to no symptoms, and normal white cell counts, except eosinophilia in two of the cases. He discovered these infiltrates while performing mass X-ray surveillance of tuberculosis patients in Zürich at the time."Zur Differential-Diagnose der Lungeninfiltrierungen | SpringerLink".
• In 1936 Löffler published 51 additional cases of the syndrome he had observed.

• In 1940, Freund and Samuelson reported 105 documented cases of Löffler syndrome, which included the 51 cases Löffler described in 1936.(Freund R, Samuelson S. Transitory infiltration of the lung with eosinophilia: Löffler’s syndrome. Arch Intern Med (Chic). 1940;66(6):1215–1220.)
• In 1942, Vogel and Minning performed human experimentation with Ascaris.(Vogel H, Minning W. Bietrage zur klinik der lungen- Ascariasis und zur Frage der fluchtigen, eosinophilen Lungeninfiltrate. Bietr. Klin Tuberk. 1942;98:620-54. Weingarten RJ. Tropical eosinophilia. The Lancet. 1943;241(6230):103-105.)

• They fed six volunteers with small amount of Ascaris eggs (6 to 45 eggs) which produced significant symptoms in five of the volunteers.
• This demonstrated an allergic element to the Löffler syndrome.

• In 1943, Weingarten published 81 cases from the coastal areas of India with a gradual onset of chronic (lasting up to years) spasmodic bronchitis, leucocytosis, massive blood eosinophilia, and X-ray of lung infiltrates in the acute phase.

• He named this syndrome ‘tropical eosinophilia’, and directly stated it to be different from the milder symptoms and transient nature of Löffler syndrome.
• Tropical eosinophilia has occasionally been referred to as Weingarten syndrome and thought to be due to an immune response to microfilariae.
• Nevertheless, plenty of clinician scientists believe that the so-called tropical eosinophilia is a mere modality of Loeffler's syndrome.

• In 1943, Maier published 100 cases of the syndrome he observed in Löffler’s clinic. He believed the lung infiltrates to be similar to the temporary infiltrations from eosinophilic pneumonia observed in asthma.
• In 1948, Löffler injected Ascaris into guinea pigs which induced the syndrome in these animals.
• In 1952, Crofton proposed the term pulmonary eosinophilia to include the range of diseases with pulmonary infiltration and blood eosinophilia.
• The classification of pulmonary eosinophilia into five groups included:

• Löffler syndrome (transient infiltrations)
• Prolonged pulmonary eosinophilia without asthma
• Prolonged pulmonary eosinophilia with asthma
• Tropical pulmonary eosinophilia usually with asthmatic symptoms
• Polyarteritis nodosa.

• Although Löffler only described eosinophilic pneumonia in the context of infection, many authors give the term "Löffler's syndrome" to any form of acute onset pulmonary eosinophilia no matter what the underlying cause. If the cause is unknown, it is specified and called "simple pulmonary eosinophilia".
• Cardiac damage caused by the damaging effects of eosinophil granule proteins (ex. major basic protein) is known as Loeffler endocarditis and can be caused by idiopathic eosinophilia or eosinophilia in response to parasitic infection.

• The most well-known case of Löffler's syndrome was in a young boy from Louisiana. He arrived at the hospital reporting a high fever after three days, as well as having rapid breathing. ”He was hospitalized and treated with supplemental oxygen, intravenous methylprednisolone, and nebulized albuterol.” The boy's symptoms quickly subsided and upon further investigation, it was discovered that the boy worked caring for pigs. A test was then performed on the pigs' fecal matter and surrounding soil; it contained the parasite that had caused the boy's ailment.
• Another incident again involved a young boy who had suffered from vomiting and a fever for a span of 3 months. When the doctors finally took an echocardiograph of the child they discovered that the “patient’s admission blood count showed leukocytosis with an abnormally elevated level of peripheral eosinophils.” The child was then diagnosed with Löffler's endocarditis and immediately began immunosuppressive therapy to decline the eosinophilic count.