|Year : 2021 | Volume
| Issue : 1 | Page : 43-47
Acne Fulminans: A Case Report and Review of Literature
Jushya Bhatia, Ankur Sarin, Kailash Bhatia
Department of Dermatology, Venereology and Leprosy, Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India
|Date of Submission||30-Dec-2018|
|Date of Decision||14-Apr-2019|
|Date of Acceptance||26-Apr-2020|
|Date of Web Publication||31-Dec-2020|
88-89 B Shanti Sadan, Gumasta Nagar, Indore - 452 009, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
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 Jan 25];22:43-7. Available from: https://www.ijpd.in/text.asp?2021/22/1/43/305802
| Introduction|| |
Acne Fulminans is the most extreme but rare presentation of the clinical spectrum of acne, primarily affecting adolescent males. While this is a well established clinical entity, <200 cases have been reported in the literature. Here, we present a report of a case of acne fulminans with the review of literature.
| Case Report|| |
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|
Click here to view
|Figure 2: Subsidence of the lesions with presence of pus points, 1 week after initiation of oral prednisolone|
Click here to view
|Figure 3: After 3 months of oral prednisolone nodules, pustules and hemorrhagic crusting have reduced. Erythema and scarring are evident|
Click here to view
|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|
Click here to view
| Discussion and Review of Literature|| |
A thorough search of literature was performed for AF using PubMed, MEDLINE, EMBASE, and UK PubMed Central electronic databases.
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., 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.,
It usually affects individuals with preexisting acne vulgaris triggered by oral isotretinoin therapy but may arise de novo.,, The mean duration of acne before the onset of AF is 2 years.
Currently, <200 cases have been reported, and the incidence seems to be declining, possibly due to earlier and better treatment of acne.
This article provides an extensive review of AF, including known pathomechanisms, clinical features, recent classification, required investigations, and treatment protocols.
Kelly and Burns first identified the acute onset of ulcerative acne conglobata with polyarthralgia in 1971. AF was initially termed as acne maligna or acute febrile ulcerative acne. Plewig and Kligman coined the term AF in 1975. 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.
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.
Kellett et al. demonstrated circulating immune complexes in two patients with AF. A fall in the circulating immune complexes accompanied clinical improvement in the patients. Williamson et al. labeled this as an Arthus reaction.
AF has been suggested to arise after oral isotretinoin therapy. Increased fragility and size of the pilosebaceous duct after isotretinoin therapy facilitates contact of the immune system with P. acnes antigens and chemoattractants. Isotretinoin initiation in a patient with acne induces inflammation in the skin, with enhanced neutrophilic burst. 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.
Genetic factors may be responsible for the occurrence of AF in some monozygotic twins. Two siblings, one developing eruptive pyogenic granuloma and the other developing AF after taking isotretinoin for severe acne, have been described. This may be explained by the tendency of retinoids to stimulate granulation tissue formation and enhance wound healing.
Testosterone use and discontinuation are also suggested as triggers. 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. 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.
Recent studies demonstrate the release of interleukin-1 by P. acnes-activated inflammasomes. This autoimmune theory is further strengthened by the rapid response of this disease to steroids.
Possible triggers for AF include oral isotretinoin therapy, antibiotic therapy (including tetracycline, lymecycline, and erythromycin), and steroids.,,
A case of AF developing after treatment of hepatitis B infection with interferon has been reported.
AF presents as sudden eruption of tender ulcers with friable, hemorrhagic crusting, tender plaques, and nodules on the skin that heal with scarring. Lesions are usually present on the trunk but may be seen elsewhere on the body. In some case reports, the face was spared or showed only mild-moderate acne lesions. Goldschmidt et al. compared 8 cases of AF with 13 previously reported cases and found that nodules were rarely seen in AF. AF may occur with other systemic features such as fever, joint pain, bone pain, headache, and body ache. Other reported features are anemia and weight loss., 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.,
Joints most commonly affected are the shoulders, hips, proximal extremities, and the axial skeleton.
Case reports exist pointing an association of AF with erythema nodosum, SAPHO syndrome, Crohn's disease, or ulcerative colitis.,,
In some patients, acne of the intensity of AF exists but without any systemic involvement. This is termed as “AF sans fulminans.”
An expert panel classified AF into four variants:
- AF with SS (AF-SS)
- AF without SS (AF-WOSS)
- Isotretinoin-induced AF with SS (IIAF-SS)
- Isotretinoin-induced WOSS (IIAF-WOSS).
These terminologies replace the older terms such as acne maligna, acute febrile ulcerative acne conglobate, AF, and pseudo-AF.
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).
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.,,
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. Corticosteroid pulse therapy with addition of oral isotretinoin after subsidence of inflammatory phase of acne has been tried.
Concomitant administration of isotretinoin and prednisolone is able to resolve systemic signs and markedly improve skin lesions.
A longer duration of isotretinoin administration is often required compared to other forms of acne.
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.
To prevent IIAF, oral corticosteroids can be initiated along with or 2 weeks before isotretinoin therapy; then, isotretinoin dose can be gradually increased.
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.
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.
Although oral steroids do not have a clear link with pseudotumor cerebri syndrome, sudden withdrawal of chronic oral corticosteroids can precipitate it.
Dapsone, methotrexate, and cyclosporine have also been tried with affirmative results but warrant larger trials.,,
Infliximab has been tried with success in a patient of SAPHO syndrome with AF after failure with prednisone, isotretinoin, cyclosporine, and methotrexate.
Similarly, Dawoud et al. reported successful treatment of AF-SS with adalimumab.
Anakinra has been used with success in two patients.
Administration of biologics in AF has no solid evidential data but is suggested in patients intolerant to isotretinoin or in recalcitrant cases.
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|| |
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Alakeel A, Ferneiny M, Auffret N, Bodemer C. Acne fulminans: Case series and review of the literature. Pediatr Dermatol 2016;33:e388-92.
Karvonen SL. Acne fulminans: Report of clinical findings and treatment of twenty-four patients. J Am Acad Dermatol 1993;28:572-9.
Grando LR, Leite OG, Cestari TF. Pseudo-acne fulminans associated with oral isotretinoin. An Bras Dermatol 2014;89:657-9.
Li AW, Antaya RJ. Isotretinoin-induced acne fulminans without systemic symptoms with concurrent exuberant granulation tissue. Pediatr Dermatol 2018;35:257-8.
Blanc D, Zultak M, Wendling D, Lonchampt F. Eruptive pyogenic granulomas and acne fulminans in two siblings treated with isotretinoin. A possible common pathogenesis. Dermatologica 1988;177:16-8.
Kelly AP, Burns RE. Acute febrile ulcerative conglobate acne with polyarthralgia. Arch Dermatol 1971;104:182-7.
Plewig G, Kligman AM. Acne fulminans. In: Acne. Berlin: Springer-Verlag; 1975. p. 342-51.
Karvonen SL, Räsänen L, Cunliffe WJ, Holland KT, Karvonen J, Reunala T. Delayed hypersensitivity to Propionibacterium acnes
in patients with severe nodular acne and acne fulminans. Dermatology 1994;189:344-9.
Kellett JK, Beck MH, Chalmers RJ. Erythema nodosum and circulating immune complexes in Acne fulminans after treatment with isotretinoin (Letter). Br Med J 1985;290:820.
Williamson DM, Cunliffe WJ, Gatecliff M, Scott DG. Acute ulcerative acne conglobata (acne fulminans) with erythema nodosum. Clin Exp Dermatol 1977;2:351-4.
Jansen T, Romiti R, Plewig G. Acute severe acne in a female patient (acne fulminans?) Br J Dermatol 1999;141:945-7.
Perkins W, Crocket KV, Hodgins MB, Mackie RM, Lackie JM. The effect of treatment with 13-cis-retinoic acid on the metabolic burst of peripheral blood neutrophils from patients with acne. Br J Dermatol 1991;124:429-32.
Makrantonaki E, Ganceviciene R, Zouboulis C. An update on the role of the sebaceous gland in the pathogenesis of acne. Dermatoendocrinol 2011;3:41-9.
Saint-Jean M, Frenard C, Le Bras M, Aubin GG, Corvec S, Dréno B. Testosterone-induced acne fulminans in twins with Kallmann's syndrome. JAAD Case Rep 2015;1:27-9.
Elson ML. The role of retinoids in wound healing. J Am Acad Dermatol 1998;39:S79-81.
Melnik B, Jansen T, Grabbe S. Abuse of anabolic-androgenic steroids and bodybuilding acne: An underestimated health problem. J Dtsch Dermatol Ges 2007;5:110-7.
Iqbal M, Kolodney MS. Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab. J Am Acad Dermatol 2005;52:S118-20.
Qin M, Pirouz A, Kim MH, Krutzik SR, Garbán HJ, Kim J. Propionibacterium acnes
Induces IL-1β secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol 2014;134:381-8.
Gualtieri B, Tonini A, Panduri S, Chiricozzi A, Romanelli M. Acne fulminans associated with lymecycline intake: A case report. Clin Cosmet Investig Dermatol 2018;11:403-5.
Didona D, Paolino G, Cantisani C, Viti G, Caposiena Caro DR, Didona B. Acne fulminans following isotretinoine therapy. G Ital Dermatol Venereol 2019;154:84-5.
Arora S, Malik A, Kumar D, Sodhi N. Hepatitis B, interferon, and acne fulminans in a young girl. Indian Dermatol Online J 2016;7:93-5.
] [Full text]
Proença NG. Acne fulminans. An Bras Dermatol 2017;92(5 Suppl 1):8-10.
Zaba R, Schwartz R, Jarmuda S, Czarnecka-Operacz M, Silny W. Acne fulminans: Explosive systemic form of acne. J Eur Acad Dermatol Venereol 2011;25:501-7.
Goldschmidt H, Leyden JJ, Stein KH. Acne fulminans: Investigation of acute febrile ulcerative acne. Arch Dermatol 1977;113:444-9.
Siadat AH, Bostakian A, Abtahi-Naeini B, Shahbazi M. Successful treatment of facial acne fulminans: Antimicrobial agents and oral prednisolone as promising regimes. Case Rep Dermatol Med 2017;2017:7092910.
Geller AS, Alagia RF. Sacroiliitis after use of oral isotretinoin-association with acne fulminans or adverse effect? An Bras Dermatol 2013;88:193-6.
Peleg H, Koslowski B, Hiller N, Heyman SN. Radiologic features of acne fulminans. Isr Med Assoc J 2014;16:393-4.
Wakabayashi M, Fujimoto N, Uenishi T, Danno K, Tanaka T. A case of acne fulminans in a patient with ulcerative colitis successfully treated with prednisolone and diaminodiphenylsulfone: A literature review of acne fulminans, rosacea fulminans and neutrophilic dermatoses occurring in the setting of inflammatory bowel disease. Dermatology 2011;222:231-5.
Meena M, Mittal A, Khare AK, Gupta LK. Pseudo Acne Fulminans: An Under Recognized Entity. Indian Dermatol Online J 2018;9:462-4.
] [Full text]
Greywal T, Zaenglein AL, Baldwin HE, Bhatia N, Chernoff KA, Del Rosso JQ, et al
. Evidence-based recommendations for the management of acne fulminans and its variants. J Am Acad Dermatol 2017;77:109-17.
Allison MA, Dunn CL, Person DA. Acne fulminans treated with isotretinoin and “pulse” corticosteroids. Pediatr Dermatol 1997;14:39-42.
Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: A review of 25 cases. Br J Dermatol 1999;141:307-9.
Massa AF, Burmeister L, Bass D, Zouboulis CC. Acne fulminans: Treatment experience from 26 patients. Dermatology 2017;233:136-40.
Bettoli V, Borghi A, Mantovani L, Scorrano R, Minghetti S, Toni G, et al
. Safe use of oral isotretinoin after pseudo-tumor cerebri due to minocycline. Eur J Dermatol 2011;21:1024-5.
Saigusa K, Takei H, Shishido T, Ohki J, Naoe N, Ohno K. Benign intracranial hypertension resulting from corticosteroid withdrawal: Case report. No Shinkei Geka 2002;30:57-62.
Rodríguez-Lomba E, Molina-López I, Monteagudo-Sáez I, Suárez-Fernández R, Campos-Domínguez M. A case of acne fulminans with sacroiliitis successfully treated with methotrexate and isotretinoin. Dermatol Ther 2016;29:476-8.
Giavedoni P, Mascaró-Galy JM, Aguilera P, Estrach-Panella T. Acne fulminans successfully treated with cyclosporine and isotretinoin. J Am Acad Dermatol 2014;70:e38-9.
Dawoud NM, Elnady BM, Elkhouly T, Yosef A. Adalimumab as a successful treatment for acne fulminans and bilateral acute sacroiliitis with hip synovitis complicating isotretinoin therapy. Indian J Dermatol Venereol Leprol 2018;84:104-7.
] [Full text]
Oranges T, Insalaco A, Diociaiuti A, Carnevale C, Strippoli R, Zambruno G, et al
. Severe osteoarticular involvement in isotretinoin-triggered acne fulminans: Two cases successfully treated with anakinra. J Eur Acad Dermatol Venereol 2017;31:e277-e279.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]