Erythema gyratum repens
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Gammel's disease.
Overview
Historical Perspective
- In 1925 Rothman wrote a comprehensive review on the subject of cutaneous manifestations in patients with malignant tumors and since then cases were added to proof for the relationship between internal neoplasm and some skin lesions.
- In 1953, the dermatologist, Dr. John A Gammel who was trained to link bizarre or recalcitrant dermatoses to internal diseases was the first one who described and labeled Erythema Granulatum Repens in a 55-year-old patient who had been complaining of pruritic scaly skin eruption and found few months later to have poorly differentiated adenocarcinoma. [1]
- Up to 1992, there were only 49 cases in the literature, 41 of which (84%) were associated with a neoplasm [2]
- EGR is associated with internal malignancy in 82% of cases. However, between 1990 and 2010, data was collected from the medical records of patients form dermatology department in University of Genoa and from databases as pubmed and medline, the conclusion of this literature review was that EGR is no longer considered as an obligate paraneoplastic syndrome. More than expected cases of EGR were found with no neoplasm association [3]
- Non-paraneoplastic EGR could be: [4]
- Idiopathic EGR
- EGR-like eruptions (different dermatologic lesions that mimic EGR)
- EGR with concomittant skin disease as:
- pityriasis rubra pilaris, psoriasis, ichthyosis, CREST, rheumatoid arthritis, tuberculosis, bullous pemphigoid, linear IgA disease, and hypereosinophilic syndrome
- Drug-induced EGR examples are:
- Azathioprine with type I autoimmune hepatitis
- Interferon given for hepatitis C virus–related chronic hepatitis [4]
Classification
- There is no established system for the classification of EGR.
Pathophysiology
- The cause of EGR has not been identified.
- Many theories suggest that EGR is due to immunologic mechanisms
- The immunologic mechanism theory is evidenced by the observed immunofluorescence patterns of IgG, C3, and C4 at the basement membrane: [5]
- Theory 1 the tumor induces antibodies that cross-react with the basement membrane of skin
- Theory 2 the tumor produces polypeptides that bind skin antigens and render them immunogenic
- Theory 3 deposition of tumor antigen-antibody complexes onto the basement membrane causes the reactive dermatitis seen in EGR
Causes
- The cause of erythema gyratum repens has not been identified.
- Different theories suggest that EGR etiology is stemmed from immunologic reaction [5]
Differentiating Erythema Gyratum Repens from Other Diseases
- EGR has a narrow differential diagnosis and it has to be differentiated from skin lesions with gyrate erythematous eruptions, such as: [5]
- Necrolytic migratory erythema (NME)
- Erythema annulare centrifugum (EAC)
- Erythema chronicum migrans
- Erythema marginatum rheumaticum [6]
Epidemiology and Demographics
- EGR is a rare dermatologic disease, usually associated with paraneoplastic neoplasm [5]
Age
- The average age of onset of EGR is in the seventh decade of life
Gender
- The male to female ratio is 2:1
Race
- EGR commonly affects Caucasians
Risk Factors
- There are no established risk factors for EGR
Screening
- There are no screening tests for EGR.
- Screening for internal malignancy should be done immediately after EGR is diagnosed.
Natural History, Complications, and Prognosis
- The majority of patients with EGR presents with severely pruritic erythematous skin lesions that appear several months prior to the malignancy diagnosis [5]
- If the underlying malignancy left untreated, the debilitating pruritus could persist until the patient dies [5]
- Prognosis depends on the type of the underlying tumor and the probability of its treatment.
Diagnosis
Diagnostic Study of Choice
- EGR is mainly diagnosed clinically by its characteristic skin lesions.
History and Symptoms
- The universal symptoms of EGR are:
- Skin eruptions
- Intense pruritus
- Other symptoms related to the associated internal malignancy are:
- Weight loss
- Anorexia
- Fatigue
- Fever
Physical Examination
- Patients with EGR presents with a rash consisting of wavy erythematous concentric bands that can be figurate, gyrate, or annular.
- The bands are arranged in parallel rings and lined by a fine trailing edge of scale, a pattern often described as “wood grained.
- The rash typically involves large areas of the body but tends to spare the face, hands, and feet and it can expand as fast as a cm a day.
- Bullae can also form from within the areas of erythema [5]
Laboratory Findings
- There are no diagnostic laboratory findings associated with EGR.
- Eosinophilia is observed in 60% of cases [5]
Imaging Findings
- There are no imaging findings associated with EGR.
- Imaging of the chest and abdomen could show malignancy findings.
Other Diagnostic Studies
- Direct immunofluorescence in some cases shows patterns of IgG, C3, and C4 at the basement membrane [5]
- The histopathologic features of EGR is non-specific.
- Biopsy specimens show the following:
- Acanthosis, mild hyperkeratosis, focal parakeratosis, and spongiosis confined to the epidermis and superficial dermis.
- Mononuclear, lymphocytic, and histiocytic perivascular infiltrate in the superficial plexus can also be seen [5]
- Thorough paraneoplastic workup includes:[7]
- Computed tomography of thorax, abdomen, and pelvis
- Positron emission tomography/computed tomography
- Upper and lower gastrointestinal endoscopy
- Tumor markers
- Blood tests including lactate dehydrogenase and QuantiFERON to exclude tuberculosis.
Treatment
Medical Therapy
- There is no treatment for EGR; the mainstay of therapy is supportive care and treating the underlying condition [5]
- Various dermatologic and immunosuppressive therapies have been used to treat EGR.
- Systemic steroids are frequently ineffective.
- Topical steroids, vitamin A, and azathioprine have also failed to relieve skin manifestations.
- Improvement of EGR, and its associated intense pruritus depends on recognition and treatment of the underlying malignancy.
- Chemotherapy can be used to treat the internal malignancy.
Surgery
- Surgical resection of the internal tumor could be recommended as part of the management of EGR.
Prevention
- There are no primary preventive measures available for [disease name].
References
- ↑ "Reorganized text". JAMA Otolaryngol Head Neck Surg. 141 (5): 428. 2015. doi:10.1001/jamaoto.2015.0540. PMID 25996397.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/https://doi.org/10.1016/0190-9622( Check
|pmid=value (help). - ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1111/j.1468-3083.2012.04663.x Check
|pmid=value (help). - ↑ 4.0 4.1 Richey PM, Fairley JA, Stone MS (2018). "Transformation from pityriasis rubra pilaris to erythema gyratum repens-like eruption without associated malignancy: A report of 2 cases". JAAD Case Rep. 4 (9): 944–946. doi:10.1016/j.jdcr.2018.07.009. PMC 6191946. PMID 30345340 PMID: 30345340 Check
|pmid=value (help). - ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 Gore M, Winters ME (2011). "Erythema gyratum repens: a rare paraneoplastic rash". West J Emerg Med. 12 (4): 556–8. doi:10.5811/westjem.2010.11.2090. PMC 3236141. PMID 22224159 PMID: 22224159 Check
|pmid=value (help). - ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID <54 https://doi.org/10.1002/1097-0142(19880801)62:3<54 Check
|pmid=value (help). - ↑ Ridge A, Tummon O, Laing M (2019). "Response to "Transformation from pityriasis rubra pilaris to erythema gyratum repens-like eruption without associated malignancy: A report of 2 cases"". JAAD Case Rep. 5 (5): 461–462. doi:10.1016/j.jdcr.2019.03.012. PMC 6510971 Check
|pmc=value (help). PMID 31111084 PMID: 31111084 Check|pmid=value (help).