Annular erythema .Annular erythema is a descriptive term that encompasses several entities characterized by erythematous annular/ring-like patterns with centrifugal spreading lesions Type of figurate erythema

Annular erythema is a descriptive term that encompasses several entities characterized by erythematous annular/ring-like patterns with centrifugal spreading lesions

Type of figurate erythema

Characteristic Lesions: active raised red border with central clearing.

Classification of cutaneous annular erythemas:
(i) Due to a specific skin disorder (e.g., psoriasis, tinea corporis).
(ii) cutaneous inflammatory reaction triggered by drugs, infections, malignancy, or unknown causes (idiopathic).


These include:
Erythema annulare centrifugum
Erythema chronicum migrans
Erythema gyratum repens
Erythema marginatum




Erythema multiforme (EM)
Annular erythema of infancy
Necrolytic migratory erythema

1. Annular erythema By Dr Ria Maria Francis

2. Content Introduction Classification Approach Erythema annulare centrifugum Erythema chronicum migrans Erythema gyratum repens Erythema marginatum Erythema multiforme (EM) Annular erythema of infancy Necrolytic migratory erythema (NME)

3. Introduction Annular erythema is a descriptive term that encompasses several entities characterized by erythematous annular/ring-like patterns with centrifugal spreading lesions Type of figurate erythema Characteristic Lesions: active raised red border with central clearing. The confluence of nearby lesions gives a polycyclic appearance

4. Basis of annular morphology Some annular lesions result from centrifugal extension of an infection from the point of inoculation Annular lesions in DLE are the result of scarring occurring within the centre of a lesion, and progression peripherally. In neoplastic conditions such as BCC, central regression can result in annular lesions. In eruptions in which an allergic process is probably involved, the annular configuration is attributed to the refractory state of the central area. Some involve an iatrogenic component, for example warts recurring at the margin of a blistered cryotherapy site.

5. Classification Classification of cutaneous annular erythemas: (i) Due to a specific skin disorder (e.g., psoriasis, tinea corporis). (ii) cutaneous inflammatory reaction triggered by drugs, infections, malignancy, or unknown causes (idiopathic). These include: Erythema annulare centrifugum Erythema chronicum migrans Erythema gyratum repens Erythema marginatum Erythema multiforme (EM) Annular erythema of infancy Necrolytic migratory erythema

6. Approach to annular erythema Differentiate between a specific dermatological disease vs. a reactive erythema. Elicit a comprehensive history Medical h/o- current and recent Medication S ymptoms of infections Symptoms of occult malignancy Knowledge of Local prevalence of diseases and therapeutics I mmunotherapy of metastatic melanoma(checkpoint inhibitors) SARS-CoV-2 infection. Decline in streptococcal infections has reduced cases of erythema marginatum. Recently identified triggers

7. Erythema annulare centrifugum (Darier’s) Synonyms Erythema perstans Erythema figuratum perstans Erythema simplex gyratum EAC is a figurate dermatitis presenting as annular or polycyclic red/pink plaques with “ trailing scale” at the advancing edge T erm “EAC” was introduced by Darier in 1916

8. Etiology Idiopathic Infantile onset -Annular erythema of infancy Infectious associations: Fungi: dermatophytes ( 48% ) , Candida, Penicillium. Viruses: poxvirus, EBV, varicella, HIV,herpes simplex, molluscum contagiosum Bacteria: Pseudomonas, Mycobacteria, streptococci, E.coli , syphilis Parasites/ectoparasites: e.g., Phthirus pubis, Ascaris lumbricoides . Drugs: Acetazolomide, Diuretics, NSAIDs, antimalarials, amitriptyline, rituximab, IFN-α/ribavirin Neoplasms: Lymphomas, leukemias, solid tumors ( paraneoplastic EAC / PEACE) Other associations: Crohn disease, pregnancy, hyperthyroidism, , hypereosinophilic syndrome.

9. Clinical features It can occur at any age,peak incidence in the fifth decade Characterized by expanding annular or polycyclic erythematous plaques, enlarging up to 2–3 mm/day, with central clearing and “ trailing scale” at the advancing edge. Sites - buttocks, thighs and upper arms Lesions may persist weeks to months . No scarring , but PIH /occasional purpura may occur.

10. Forms of EAC

11. S uperficial form with dermal perivascular lymphohistiocytic infiltrates; note the tight “coat sleeve”-like appearance of the infiltrate

12. Differential diagnosis Fungal: Tinea corporis Connective tissue disorders: Subacute cutaneous lupus erythematosus Granulomatous: Annular sarcoidosis, Granuloma annulare, Granuloma faciale Metabolic/Paraneoplastic: Necrolytic migratory erythema, Erythema gyratum repens, Erythema marginatum Neoplastic: Cutaneous T-cell lymphoma Inflammatory/Drug-related: Drug eruptions, Erythema multiforme Autoimmune bullous disorders: Linear IgA bullous dermatosis,BP

13. Management Investigations 1.Fungal culture: skin and nails if dermatophyte infection is suspected. 2. Histopathology : Skin biopsy: confirm diagnosis & exclude differential diagnoses. Direct immunofluorescence: helps r/o autoimmune bullous disorders 3. Laboratory tests Blood tests: full blood count, liver and thyroid function tests. Autoimmune markers: antinuclear antibody (ANA) profile. Other serology: HIV testing, serum ACE (for sarcoidosis).

14. Treatment First line Identify and treat any underlying condition Steroids: moderately potent /potent topical steroids or topical calcipotriol Second line Topical tacrolimus Phototherapy Third line Chloroquine or hydroxychloroquine Systemic steroids

15. Erythema marginatum Synonyms Erythema marginatum rheumaticum Erythema annulare rheumaticum It is a migratory , annular, polycyclic, serpiginous erythematous eruption. Rare but specific cutaneous manifestation of acute rheumatic fever ( 10% of cases ) One of Duckett Jones major criteria for RF diagnosis along with carditis, migratory polyarthritis, chorea, and subcutaneous nodules.

16. Epidemiology Incidence – more in Developing countries Incidence declines as socioeconomic conditions improve. Age – more common in children of ages 5 - 15 years. Sex - no sex predilection Associated diseases Rheumatic fever ( grp A β-hemolytic streptococcal pharyngeal infection ) Psittacosis Angioedema (C1 inhibitor deficiency acquired or hereditary)

17. Pathogenesis Exact mechanism-Unknown Likely due to abnormal immune response to antigens from group A β- hemolytic streptococci (e.g., M protein). Molecular mimicry: cross-reaction with human proteins such as myosin, actin, tropomyosin,etc Bacterial factors: Certain strains with high M protein content and enhanced expression of cysteine proteases may increase virulence and cardiotoxicity .

18. Clinicial Presentation Latency: Appears 2–5 weeks after streptococcal pharyngitis. Lesion type: Erythematous macules spreading peripherally to form plaques with r aised red edges with central clearing Blanches on pressure, transient and migratory Distribution: Trunk (MC), axillae, proximal extremities; face spared Duration: Lesions last hours to days ; recurrent crops occur over weeks.

19. Differentials & Complications Differentials: Annular urticaria, including urticaria multiforme Annular erythema of infancy Erythema multiforme. Major complication: Carditis in 30–45% of patients may progress to chronic RHD with permanent valvular damage

20. Management Investigations Laboratory tests: Inflammatory markers: ESR, CRP, ferritin Throat swab & antistreptolysin O (ASO) titre Psittacosis serology Blood cultures Cardiac evaluation: ECG,Echocardiography (In presence of murmur ) Other investigations: Skin biopsy + DIF ( usually negative ) Investigations are mainly for diagnosis of underlying disease / complications.

21. Treatment There is no specific therapy for this dermatosis. Its clinical course is unaltered by treatment of the underlying acute RF however symptoms are usually mild and lesions resolve spontaneously First line for RF Aspirin or non-steroidal anti-inflammatory drugs Penicillin or erythromycin

22. Erythema Chronicum Migrans Synonyms: Erythema chronicum migrans Lyme borreliosis (early stage) Lyme disease (early stage) Erythema migrans represents the initial cutaneous manifestation of Lyme disease (60%–80%) Annular erythema develops at the site of the bite of a Borrelia infected tick

23. Causative agent This disorder is caused by a bite from a tick of the genus Ixodes and infection by the Borrelia burgdorferi spirochete Causative organisms B. burgodorferi (MC) B. afzelii . B. garinii . Ixodid tick

24. Epidemiology Distribution: Worldwide; common in US & northern/eastern Europe. Reservoirs: Mice, chipmunks, birds; deer maintain tick life cycle. Risk groups: Outdoor exposure in fields/woods. Pathogenesis B. burgdorferi uses tick salivary protein Salp15 to evade antibody killing and suppress adaptive immunity. After entry, it triggers innate and adaptive responses, but the organisms resist clearance & disseminate widely

25. Clinical presentation Stages: Early localized d/s – appearance of erythema migrans . Early disseminated disease – multiple smaller lesions c/c disease – arthritis, neurologic/cardiac complications. Lesions develops 7–15 days after tick bite Expanding (≥5 cm in diameter) annular plaque with central clearing / “bull’s-eye” appearance Site: trunk, axilla, groin, popliteal fossa. Bull’s eye appearance at site of bite

26. Systemic Manifestations & Complications Systemic Manifestations (Early Phase): Influenza-like symptoms (fatigue, headache, fever, arthralgia, myalgia), lymphadenopathy, conjunctivitis, hepatitis. Complications if Untreated: ~60%: mono-/oligoarticular arthritis (usually knee) ~10%: neurologic involvement (facial nerve palsy most common) ~5%: cardiac complications (AV block)

27. Clinical Variants of Lyme Disease Secondary ECM: ~20% of patients; smaller, less migratory lesions; may include malar erythema, maculopapular rash, or urticaria. Lymphocytoma Cutis: Solitary nodule on earlobe or breast; serology positive; resolves with antibiotics. Acrodermatitis Chronica Atrophicans (ACA): Late manifestation; violaceous, atrophic plaques on hands, feet, knees, elbows; may involve arthritis or neuropathy; responds to antibiotics. Lyme Neuroborreliosis: Cranial nerve palsies, peripheral neuropathy, meningitis, encephalopathy. Subclinical Infection: Antibodies present without symptoms; risk of late complications.

28. Pathology of Erythema Migrans Histology resembles deep gyrate erythema but is often nonspecific . Common findings: superficial and deep lymphoid infiltrates with occasional eosinophils and plasma cells . Immunohistochemistry: decreased Langerhans cells in the epidermis; dermal infiltrate contains macrophages, CD4+ T cells, and CD45RO+ memory T cells . PCR on tissue can confirm presence of Borrelia spirochetes

29. Management Tick Removal- Remove attached ticks mechanically with tweezers (including head). Early Localized Disease (Erythema Migrans ) First-line oral antibiotics: doxycycline, amoxicillin, or cefuroxime for 14–21 days Second-line: azithromycin. Disseminated/Systemic Disease ( Longer treatment needed) Neuroborreliosis or cardiac disease: IV ceftriaxone or benzylpenicillin. Oral doxycycline may be an alternative in mild cases.

30. Prevention Protective clothing, insect repellents.,Careful skin inspection after outdoor activity ,Prompt removal of ticks. Prophylaxis (High-risk tick bite) High-risk = endemic area or tick attached >36 hrs. Give single-dose doxycycline (200 mg) within 72 hrs.

31. Erythema gyratum repens Synonym: Gammel disease Erythema gyratum repens is a migratory figurate erythema characterized by concentric, wave-like “wood-grain” rings on the skin. It represents a paraneoplastic phenomenon, most commonly associated with lung carcinoma .

32. Epidemiology and Associations Age -Older than 40 years Sex –M:F ratio is 2 : 1. Ethnicity - occur predominantly in white persons Association: Considered a paraneoplastic eruption (≈80% of cases) Occurring from 1 year prior to 1 year post diagnosis of cancer Most common: Lung cancer (47%) Others: Esophagus, breast, stomach, kidney, cervix, pharynx, bladder, uterus, pancreas, prostate, and hematological cancers Pathogenesis : Immune reaction with cross-reactivity between tumor-associated antigens and skin antigens .

33. EGR in absence of malignancy Seen in association with: Dermatoses: PRP,Ps, ichthyosis. Infections: mycobacterial infections. AI/CTD: LE, Sjögren syndrome,RA, scleroderma, hypereosinophilic syndrome. Other cutaneous disorders: immunobullous diseases,MF, urticarial vasculitis, neutrophilic dermatoses. Clinicopathological correlation is essential , and malignancy screening is warranted due to the strong possibility of underlying malignancy

34. Pathogenesis Likely represents an immune reaction with cross-reactivity between tumor-associated antigens and skin antigens . Direct immunofluorescence in some cases shows IgG and C3 deposits in the skin basement membrane zone (BMZ), occasionally mirrored in the tumor. Tumor-induced modifications in the BMZ may trigger an immune response , with similar antigens in the skin causing the eruption. Histology often shows accumulation of active Langerhans cells in the upper epidermis. Glutamine metabolism in the skin has been recently suggested as contributing to the characteristic lesion pattern.

35. Clinical Presentation Presents as multiple concentric, wave-like red bands over the body, forming a distinctive “wood-grain” or “zebra-like” pattern. Lesions show sequential “rings within rings,” with the leading edge migrating about 1 cm per day. Scaling and severe pruritus are common,collarette scale may be seen Site: initially limbs and can involve the entire torso . a/w hyperkeratosis of palms, ichthyosis or bullae. Wood-grain appearance Concentric rings with collarette scaling

36. Differential diagnosis Other figurate erythemas . (EAC ,EM,NCM) Resolving Pityriasis rubra pilaris Erythrokeratodermia variabilis et progressive Autoimmune bullous diseases : BP ,EBA Cutaneous lymphomas : mycosis fungoides. Resolving psoriasis and Subacute annular ( Lapière ) variant of psoriasis Drug reactions : hypersensitivity to azathioprine. Vasculitides : urticarial vasculitis, small vessel vasculitis. AI connective tissue diseases : subacute cutaneous LE (LE gyratus repens), Sjögren, neutrophilic dermatosis. Infectious mimickers : tinea imbricata (endemic in maritime and Southeast Asia).

37. Management Investigations Autoimmune screen: Antinuclear antibody profile Malignancy screening: Chest X-ray, CT thorax/abdomen/pelvis Mammogram, cervical smear, prostate-specific antigen Endoscopy/colonoscopy (if indicated) PET scan (for occult malignancy) Treatment- identification and treatment of underlying malignancy EGR resolves when the associated neoplasm is successfully treated. There may be a return of cutaneous lesions during metastases or local recurrences

38. Annular erythema of infancy It is a rare, benign, self-limiting dermatosis seen in young children Characterized by asymptomatic, annular or polycyclic erythematous plaques with a scaly edge that resolve spontaneously without systemic involvement or sequelae. There is uncertainty whether annular erythema of infancy (AEI) is a distinct condition or a pediatric form of erythema annulare centrifugum (EAC).

39. Clinical presentation Onset can be in infancy or teenage years . Lesions identical to EAC- asymptomatic, erythematous, maculopapular plaques that enlarge into polycyclic, annular lesions with central clearing. Duration: Individual lesions last days to weeks. Cyclical pattern: New lesions may appear every 5–6 weeks. Lesions resolve spontaneously within weeks, complete resolution within first year of life . no scarring or pigmentation seen

40. Associated organisms: Candida albicans (heavy intestinal colonisation) Epstein–Barr virus Malassezia infections Differential diagnosis Familial annular erythema Urticaria Erythema gyratum atrophicans Neonatal lupus erythematosus Erythema chronicum migrans Tinea corporis Mycosis fungoides Annular lichenoid dermatitis of youth

41. Management Investigations : Microscopy and culture of skin scrapings Antinuclear antibody (ANA) testing Electrocardiogram (ECG) Skin biopsy Serology for Lyme disease Treatment First line Any associated infection should be treated Second line Potent topical steroids Third line Topical tacrolimus

42. Necrolytic migratory erythema Synonyms and inclusions Glucagonoma syndrome Pancreatic islet cell tumour Pseudoglucagonoma syndrome Pancreatic neuroendocrine tumours Paraneoplastic skin eruption most commonly associated with pancreatic neuroendocrine tumors (NETs) ( α- cell pancreatic islet cell tumors ) hallmark cutaneous manifestation of glucagonoma

43. Etiology The tumors responsible for NME are called glucagonomas , which secrete glucagon. The skin eruption precede the diagnosis of glucagonoma by several years and can be misdiagnosed as atypical eczema or psoriasis. The classic triad of unusual dermatosis, recent-onset diabetes, and weight loss should raise suspicion

44. Pseudoglucagonoma syndrome Pseudoglucagonoma syndrome can produce similar eruptions without a glucagon-secreting tumor associated with pancreatic insufficiency celiac disease intestinal malabsorption IBD cirrhosis non-pancreatic malignancies myelodysplastic syndrome.

45. Pathogenesis The pathogenetic mechanism of NME is not certain Possible mechanisms include Amino Acid Deficiency: High glucagon levels  deficiencies in amino acids, (histidine and tryptophan) contributing to NME. Malabsorption/Protein Loss: Intestinal protein loss or malabsorption Other Nutrient Deficiencies: Essential fatty acid & zinc deficiencies may contribute Therapeutic Insight: Amino acid infusions can resolve the eruption Surgical removal of the causative tumor or correction of malabsorption leads to resolution of skin changes.

46. Histopathology of Necrolytic Migratory Erythema (NME): Biopsy Site: Taken from the edge of early lesions; serial biopsies may be needed due to lesion evolution. Epidermal Changes: Parakeratosis, loss of granular layer, necrosis, separation of papillary epidermis, vacuolar degeneration, dyskeratotic keratinocytes, and neutrophilic infiltration. Early Lesions: Superficial perivascular inflammation, minor spongiosis, dyskeratotic or vacuolated epidermal cells. Dermal Changes: Mild perivascular lymphocytic and histiocytic infiltrate. Older Lesions: Dyskeratosis, acanthosis, and dermal lymphocytic infiltrate. Direct Immunofluorescence: Staining of apoptotic keratinocytes with immunoglobulins, fibrinogen, and C3. Comparison: Histology resembles changes seen in acute zinc deficiency, with basal layer cell degeneration and cleft/vesicle formation.

47. Clinical presentation Patients present with weight loss, anaemia, glucose intolerance, diarrhoea, malaise Skin Lesions Initial : itchy or tender expanding erythematous annular eruptions with crusted/eroded edges. Distribution: mainly flexural areas Mucosal Involvement- Angular cheilitis & painful, beefy- colored glossitis (1/3 rd ) Systemic Manifestations Neurological or psychiatric disturbances (in ~20% ) Complications Thromboembolic events:PE , DVT Rare: dilated cardiomyopathy.

48. Clinical Variant of NME: Necrolytic Acral Erythema (NAE) Well-demarcated lesions on acral sites Diagnosed by positive hepatitis C serology & normal glucagon levels Disease Course and Prognosis ~50% of glucagonoma patients  metastases at Dx (liver, lymph nodes, bone, lungs). Skin Changes resolves after tumor removal or somatostatin analogue therapy (e.g., octreotide).

49. Management Investigation Laboratory Tests: glucose, serum glucagon level. Imaging: USG abd ; CT-chest, abdomen & pelvis; PET scan; coeliac axis angiography; SPECT. Specialized Imaging: Somatostatin receptor imaging using ¹¹¹In-octreotide, useful for detecting neuroendocrine tumors (NETs).

50. Treatment

51. Erythema multiforme Synonym: Erythema multiforme minor Erythema multiforme von Hebra Erythema multiforme is an immune-mediated disease characterized by target lesions that can occur anywhere on the skin and mucous membranes

52. Precipitating factors Most Common Associations: Preceding herpes simplex virus (50% of cases) or Mycoplasma infection, especially with eye involvement.

53. Forms of erythema multiforme

54. Clinical Presentation Skin lesions Typical target lesion: . At least 3 zones : dusky red centre surrounded by pale zone, which is surrounded by outer red ring.well defined borders Resembles a “bull’s eye/iris” lesion . Atypical papular target lesions: Only 2 zones and/or poorly defined border. Numerous lesions on Dorsum of hands, forearms (MC),trunk. May occur in areas of sunburn or trauma ( Koebner phenomenon ). Mucosa: buccal mucosa, lips (crusted), less often ocular & genital mucosa

55. Systemic symptoms EM minor: absent or mild. EM major: fever, malaise, arthralgia with joint swelling. Rare systemic involvement: pulmonary, renal, hepatic, hematologic changes. Rare variants: Persistent EM (lesions remain for weeks–months). Continuous EM (lesions develop almost continuously). Blaschkoid EM (along Blaschko’s lines). EM-like lesions in acute generalised exanthematous pustulosis . Rowell syndrome : lupus erythematosus with EM-like lesions and immunological markers (ANA, anti-Ro/La, RF).

56. Natural history and Course Natural history Lesions appear within 24 hrs , fully developed in 72 hrs . Remain fixed for ≥7 days, heals without scarring. Sequelae: sometimes post-inflammatory hyper/hypopigmentation; rarely ocular damage in EM major. Course & Recurrence Recurrences are common in HSV-associated cases . Typically 1–2 episodes/year ; may be seasonal. In immunosuppressed or on steroids → more frequent ( 5–6/year) or continuous overlapping disease. Corticosteroid use may also increase risk of secondary bacterial infections . Rarely, persistent EM with protracted course lasting months.

57. Differential diagnosis Giant annular urticaria often mislabeled as EM. “Urticaria multiforme” (a childhood urticaria variant) can mimic EM. Key clinical distinctions between EM & urticaria: EM lesions: fixed at same site ≥7 days; central epidermal damage (crust/vesicle). Urticaria lesions: transient (<24 hrs ); center normal or erythematous, Other Mimickers of EM (“target-like” /targetoid lesions): Fixed drug eruption Kawasaki disease (especially in children). Erythema Annulare Centrifugum . Sweet syndrome . Vasculitis (esp. urticarial vasculitis). SLE: Rowell syndrome shows EM-like lesions. Photosensitive eruptions :PMLE , juvenile spring eruption.

58. Management 1. General Principles: depends on extent and severity of disease. Localized bullous EM : may be self-limiting or treated with topical corticosteroids . Widespread disease: may require oral corticosteroids . Ocular involvement: requires early ophthalmology referral . 2. Systemic Corticosteroids Provide relief of systemic symptoms (e.g., fever). Typical dosage for severe cases: Prednisolone 30–60 mg/day , tapered over 1–4 weeks. 3. Antiviral Therapy (HSV-associated EM) Acyclovir or other antivirals are ineffective once eruption appears . Long-term prophylaxis is helpful for recurrent EM: Typical dosage: 200 mg three times daily Some patients without overt HSV infection may still benefit, suggesting subclinical HSV involvement . May prevent recurrent polyarthritis associated with EM. 4. Other therapies for Recurrent or Idiopathic EM Thalidomide( prevent relapses), Immunosuppressants: Dapsone,Azathioprine,MMF,Cyclosporin

59. Condition Clinical feature Underlying cause Management Erythema Annulare Cenrifugum (EAC) Annular erythematous plaque with trailing scale and slowly advancing lesions Multifactorial ( Inf,drugs,AI d/ s,CA ) Self limited. Treat underlying cause Erythema Gyratum Repens(EGR) Lesions wood-grain type and migrate more quickly than EAC Closely associated with malignancy Diagnosis and management of underlying malignancy Erythema Chronicum Migrans Annular erythema arising at location of tick bite Lyme’s disease Doxycyline 100mg BD for 2-3 wks. Erythema Marginatum Rheumaticum Asymptomatic annular/polycyclic, erythematous eruption. Transient & migratory Acute rheumatic fever Self resolving . Treat underlying RF

60. Conclusion Annular dermatoses represent a large, heterogeneous group of conditions. Accurate diagnosis requires: Detailed history (including past dermatological diseases). Careful analysis of clinical presentation (a/c vs c/c, isolated vs multiple, erythema vs purpura). H istopathological findings. Annularity is dynamic – lesions can evolve and change over time or between visits. Patients should be asked if they have photographs of lesions from early stages to aid diagnosis. Differential diagnosis must always consider the wide range of other annular dermatoses .