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CASE REPORT
Year : 2021  |  Volume : 22  |  Issue : 1  |  Page : 43-47

Acne Fulminans: A Case Report and Review of Literature


Department of Dermatology, Venereology and Leprosy, Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India

Date of Submission30-Dec-2018
Date of Decision14-Apr-2019
Date of Acceptance26-Apr-2020
Date of Web Publication31-Dec-2020

Correspondence Address:
Jushya Bhatia
88-89 B Shanti Sadan, Gumasta Nagar, Indore - 452 009, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_141_18

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  Abstract 


Acne fulminans (AF), a variant of acne vulgaris, is a rare disease that occurs after treatment of AF with oral isotretinoin. Less than 200 cases of AF have been reported in literature, mostly in young men and all with varying clinical presentations. A thorough search of literature was performed for AF using PubMed, MEDLINE, EMBASE, and UK PubMed Central electronic databases. Pathogenesis is not clearly established. However, it is most likely due to hypersensitivity reactions to sebum or bacterial antigens. It presents as sudden eruption of friable, hemorrhagic crusting overlying the ulcers, plaques, and tender nodules, usually on the trunk, with or without systemic symptoms such as malaise, fever, and arthralgia a few days after initiation of oral isotretinoin therapy. Laboratory abnormalities including raised erythrocyte sedimentation rate, altered hematological profile, and radiological evidence of osteolytic bone lesions may be found. Treatment involves the use of oral steroids with subsequent addition of oral isotretinoin. Many other immunosuppressive therapies have been tried.

Keywords: Acne fulminans, isotretinoin, prednisolone


How to cite this article:
Bhatia J, Sarin A, Bhatia K. Acne Fulminans: A Case Report and Review of Literature. Indian J Paediatr Dermatol 2021;22:43-7

How to cite this URL:
Bhatia J, Sarin A, Bhatia K. Acne Fulminans: A Case Report and Review of Literature. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Apr 22];22:43-7. Available from: https://www.ijpd.in/text.asp?2021/22/1/43/305802




  Introduction Top


Acne Fulminans is the most extreme but rare presentation of the clinical spectrum of acne, primarily affecting adolescent males.[1] While this is a well established clinical entity, <200 cases have been reported in the literature.[2] Here, we present a report of a case of acne fulminans with the review of literature.


  Case Report Top


An 18-year-old male presented with multiple painful pustules and weeping ulcers with hemorrhagic crusting over few lesions over both cheeks and forehead along with the development of cysts. This was accompanied by fever, arthralgia, and lethargy. The patient was admitted for supervision. Complementary investigations revealed leukocytosis with neutrophilia and elevated erythrocyte sedimentation rate (ESR). Radiographic imaging revealed no bone involvement. A history of oral isotretinoin intake for acne for 14 days before the onset of symptoms was present. A diagnosis of acne fulminans (AF) was made, and oral isotretinoin was withheld, suspecting it as a trigger. Oral prednisolone (1 mg/kg) was instituted. Oral amoxicillin-clavulanic acid 1 g twice daily for 7 days, potassium permanganate compresses twice daily, oral paracetamol, and aceclofenac were added. The cysts were drained and liquid nitrogen cryotherapy was done on nodules. Oral prednisolone was tapered over 3-month duration in which the patient showed considerable improvement with no symptoms or signs of relapse [Figure 1],[Figure 2],[Figure 3],[Figure 4]. Isotretinoin was re-introduced at 20 mg/day after 4 weeks of starting oral steroids and was continued for 5 months, during which the lesions did not flare. At the 12th month follow-up after discontinuation of oral isotretinoin, the patient did not report any new lesions.
Figure 1: Nodules and hemorrhagic crusting in the patient with acne fulminans

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Figure 2: Subsidence of the lesions with presence of pus points, 1 week after initiation of oral prednisolone

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Figure 3: After 3 months of oral prednisolone nodules, pustules and hemorrhagic crusting have reduced. Erythema and scarring are evident

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Figure 4: Three months after stopping oral prednisolone and continuing with oral isotretinoin, the patient shows a decrease in acne lesions but with persistent scarring

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  Discussion and Review of Literature Top


Method

A thorough search of literature was performed for AF using PubMed, MEDLINE, EMBASE, and UK PubMed Central electronic databases.

Introduction

AF, described as the most extreme but rare presentation of the clinical spectrum of acne, primarily affects adolescent males. It has also been reported in females.[1],[2] It is an acute condition characterized by abrupt onset of large, inflammatory plaques, nodules, erosions, and ulcers with hemorrhagic crusting usually on the back, chest, and face. Systemic symptoms (SS) such as fever, joint pain, and bone pain may be present. Elevated white cell count and inflammatory markers in the blood, radiological evidence of bone involvement including osteolytic bone lesions, may accompany cutaneous lesions.[1],[2]

It usually affects individuals with preexisting acne vulgaris triggered by oral isotretinoin therapy but may arise de novo.[3],[4],[5] The mean duration of acne before the onset of AF is 2 years.[2]

Currently, <200 cases have been reported, and the incidence seems to be declining, possibly due to earlier and better treatment of acne.[2]

This article provides an extensive review of AF, including known pathomechanisms, clinical features, recent classification, required investigations, and treatment protocols.

History

Kelly and Burns first identified the acute onset of ulcerative acne conglobata with polyarthralgia in 1971.[6] AF was initially termed as acne maligna or acute febrile ulcerative acne. Plewig and Kligman coined the term AF in 1975.[7] It is derived from a Latin word “Fulmen,” meaning lightning, which highlights its characteristic abrupt onset and severity and segregates these patients from those with acne conglobata that has a different course and prognosis.

Pathomechanisms

The pathogenesis is not clearly known. Multiple hypotheses have been put forth. One theory suggests hypersensitivity to sebum or bacterial antigens. Circulating antibodies and specific cell-mediated immunity to Propionibacterium acnes are elevated in severe acne including AF.[8]

Kellett et al. demonstrated circulating immune complexes in two patients with AF.[9] A fall in the circulating immune complexes accompanied clinical improvement in the patients. Williamson et al. labeled this as an Arthus reaction.[10]

AF has been suggested to arise after oral isotretinoin therapy.[1] Increased fragility and size of the pilosebaceous duct after isotretinoin therapy facilitates contact of the immune system with P. acnes antigens and chemoattractants.[11] Isotretinoin initiation in a patient with acne induces inflammation in the skin, with enhanced neutrophilic burst.[12] This increased inflammation or the patient's response to it may lead to AF. Apoptosis of sebocytes due to isotretinoin with the abundant release of cytokines may intensify the degree of inflammation.[13]

Genetic factors may be responsible for the occurrence of AF in some monozygotic twins.[14] Two siblings, one developing eruptive pyogenic granuloma and the other developing AF after taking isotretinoin for severe acne, have been described.[5] This may be explained by the tendency of retinoids to stimulate granulation tissue formation and enhance wound healing.[15]

Testosterone use and discontinuation are also suggested as triggers.[14] There is substantial evidence linking testosterone therapy, with or without elevated serum testosterone, to AF. Similarly, Melnik et al. reported a case of AF in a bodybuilder self-medicating on testosterone and anabolic steroids.[16] Physiological testosterone upsurge during puberty may explain inclination of this disease toward adolescent males. Furthermore, anabolic steroids increase sebum excretion rate and the population density of P. acnes.

An association with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and its response to infliximab suggests that increased inflammatory cytokines, especially tumor necrosis factor-α, could play a role in AF.[17]

Recent studies demonstrate the release of interleukin-1 by P. acnes-activated inflammasomes.[18] This autoimmune theory is further strengthened by the rapid response of this disease to steroids.

Clinical presentation

Possible triggers for AF include oral isotretinoin therapy, antibiotic therapy (including tetracycline, lymecycline, and erythromycin), and steroids.[3],[19],[20]

A case of AF developing after treatment of hepatitis B infection with interferon has been reported.[21]

AF presents as sudden eruption of tender ulcers with friable, hemorrhagic crusting, tender plaques, and nodules on the skin that heal with scarring.[22] Lesions are usually present on the trunk but may be seen elsewhere on the body.[23] In some case reports, the face was spared or showed only mild-moderate acne lesions.[24] Goldschmidt et al. compared 8 cases of AF with 13 previously reported cases and found that nodules were rarely seen in AF.[24] AF may occur with other systemic features such as fever, joint pain, bone pain, headache, and body ache.[23] Other reported features are anemia and weight loss.[24],[25] Laboratory changes such as anemia, leukocytosis, raised ESR, or C-reactive protein (CRP) and radiological abnormalities such as osteolytic changes in the bones may be evident in some patients.[23],[26]

Joints most commonly affected are the shoulders, hips, proximal extremities, and the axial skeleton.[27]

Case reports exist pointing an association of AF with erythema nodosum, SAPHO syndrome, Crohn's disease, or ulcerative colitis.[1],[10],[28]

In some patients, acne of the intensity of AF exists but without any systemic involvement. This is termed as “AF sans fulminans.”[29]

Classification

An expert panel classified AF into four variants:[30]

  1. AF with SS (AF-SS)
  2. AF without SS (AF-WOSS)
  3. Isotretinoin-induced AF with SS (IIAF-SS)
  4. Isotretinoin-induced WOSS (IIAF-WOSS).


These terminologies replace the older terms such as acne maligna, acute febrile ulcerative acne conglobate, AF, and pseudo-AF.

Investigations[30]

In a susceptible patient, a basic laboratory and radiographic workup are necessary to assess systemic involvement. The following tests are suggested:

  • Complete blood counts with differential counts
  • Liver function tests
  • ESR and CRP
  • Serum cholesterol and triglycerides
  • Urine or serum pregnancy test (in women)
  • Radiograph or bone scan (if symptoms suggestive of bone or joint involvement are present).


Treatment

There is a lack of clearly defined guideline to approach treatment of AF. It responds poorly to oral antibiotics alone. Response to oral corticosteroids is dramatic. Addition of oral isotretinoin enhances the effect of corticosteroids and reduces the time of resolution of the disease.[1],[2],[31]

Seukeran and Cunliffe compared various therapeutic regimens in 25 patients of AF. Oral antibiotics alone were shown to provide slow relief. Addition of systemic steroids provided quicker resolution of SS, but the time to clearance of acne was longer than when combined with oral isotretinoin in the 4th–6th week. Early administration of corticosteroids provided faster control of systemic features.[32] Corticosteroid pulse therapy with addition of oral isotretinoin after subsidence of inflammatory phase of acne has been tried.[31]

Concomitant administration of isotretinoin and prednisolone is able to resolve systemic signs and markedly improve skin lesions.[33]

A longer duration of isotretinoin administration is often required compared to other forms of acne.[1]

Recently, an expert panel recommended initiating prednisone 0.5–1 mg/kg/day as monotherapy for at least 4 weeks and 2 weeks in AF-SS and AF-WOSS, respectively, and continuing till the crusted lesions have healed. Then, low-dose isotretinoin (0.1 mg/kg/day) should be added, and corticosteroids continued concurrently with it for 4 weeks. Following this, corticosteroids can be tapered and the dose of isotretinoin increased. Corticosteroid dose can be halved every other week up to the physiological dose and then continued on alternate days for 2 weeks. In patients with IIAF-SS and IIAF-WOSS also, the above regimen is followed along with discontinuation of oral isotretinoin till the lesions of AF have healed completely.[30]

To prevent IIAF, oral corticosteroids can be initiated along with or 2 weeks before isotretinoin therapy; then, isotretinoin dose can be gradually increased.[30]

Antibiotics are generally not effective. If they are prescribed, as in case of intolerance to oral corticosteroids or isotretinoin, then, the maximum dose of tetracyclines is prescribed, i.e., doxycycline 100 mg twice daily, minocycline 100 mg twice daily, and tetracycline 500 mg to 1 g twice daily.[2]

Antibiotics such as that of the tetracycline group should be avoided with isotretinoin due to the risk of secondary pseudotumor cerebri syndrome, the highest risk being with minocycline.[34]

Although oral steroids do not have a clear link with pseudotumor cerebri syndrome, sudden withdrawal of chronic oral corticosteroids can precipitate it.[35]

Dapsone, methotrexate, and cyclosporine have also been tried with affirmative results but warrant larger trials.[28],[36],[37]

Infliximab has been tried with success in a patient of SAPHO syndrome with AF after failure with prednisone, isotretinoin, cyclosporine, and methotrexate.[17]

Similarly, Dawoud et al. reported successful treatment of AF-SS with adalimumab.[38]

Anakinra has been used with success in two patients.[39]

Administration of biologics in AF has no solid evidential data but is suggested in patients intolerant to isotretinoin or in recalcitrant cases.[30]

Supportive therapy in the form of surgical debridement, potassium permanganate or saline compresses, antiseptic and antibacterial cleansers, short duration of topical corticosteroids, and pulsed dye laser therapy can be added depending on patient requirement.


  Conclusion Top


AF is a scarring form of acne vulgaris that presents with cutaneous findings with or WOSS. Cutaneous features include eruptive, friable lesions with ulcers, tender nodules, and plaques, usually on the back, upper chest, buttocks, and face. The patient can present with constitutional symptoms, elevated inflammatory markers, and osteolytic bone involvement.

The disease may arise de novo or may follow isotretinoin therapy, testosterone introduction, or withdrawal or use of anabolic steroids. Pathogenesis is not clear though many theories including hypersensitivity to sebum or P. acnes have been proposed.

Treatment should involve the early introduction of oral steroids with the addition of oral isotretinoin after 4–5 weeks.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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