INTRODUCTION

An exanthem is a rash that appears suddenly, spreads within several hours, and resolves within a few days. It consists of erythematous macules that may be associated with other primary lesions (papules, plaques, vesicles, purpura, or even necrosis). Its etiologies are numerous, primarily viral in children and drug-related in adults. However, in rare situations, it may be the manifestation of a life-threatening condition or a public health emergency. Herein, we report a case of a maculopapular exanthema revealing acute cholecystitis.

CASE REPORT

A 39-year-old patient, with no notable pathological history, was hospitalized for the management of a maculopapular rash that had been evolving for ten days, preceded two days earlier by a fever of 41°C and headaches complicated by confusion. A clinical examination revealed a stable patient in terms of hemodynamics and respiration, febrile at 40°C. A dermatological examination showed a maculopapular exanthem on the trunk and limbs, sparing the face, with some purpuric petechial lesions on the lower third of the legs extending to the dorsal aspect of the feet, along with edema of the lower limbs with slight pitting (Figs. 1a – 1d). We also noted the presence of conjunctival hyperemia and jaundice.

Figure 1: (a) Anterior view of the maculopapular exanthema on the trunk. (b) Posterior view of the trunk showing the maculopapular exanthema. (c) Anterior view of the lower limbs showing exanthema associated with purpuric lesions. (d) Lateral view of maculopapular exanthema on the trunk.

Other mucous membranes were healthy, and the lymph nodes were free. An abdominal examination was unremarkable. We initially considered drug-induced toxic dermatitis, followed by viral causes (primary HIV infection, CMV, EBV, hepatitis), secondary syphilis, rickettsiosis, and leptospirosis.

Biological tests revealed a major inflammatory syndrome (C-reactive protein: 141.6 mg/L), and the blood count showed leukocytosis (20,240 elements/mm³) with a neutrophilic predominance. Liver function tests were disturbed: ASAT at 277 (9 times the normal), ALAT at 144 (4 times the normal), gamma-GT at 101.06 U/L, total bilirubin at 14.52 mg/L, indirect bilirubin at 9.52 mg/L, direct bilirubin at 5 mg/L (normal < 3), and alkaline phosphatase at 99.35 U/L. Three positive blood cultures for E. coli, hepatitis B and C serologies, syphilis, and HIV tests, as well as blood cultures, were negative.

A skin biopsy suggested leukocytoclastic vasculitis. Abdominal ultrasound revealed acute cholecystitis. After consultation with gastroenterologists and visceral surgeons, we established the diagnosis of a maculopapular exanthem associated with septicemia complicating acute cholecystitis. The patient was started on intravenous ciprofloxacin 200 mg twice daily, along with a dermocorticosteroid preparation and monitoring of liver function tests. Clinical and biological evolution showed fever resolution by day three of treatment, with the beginning of regression of the skin lesions, jaundice (Figs. 2a and 2b) and normalization of C-reactive protein. The patient was scheduled for cholecystectomy after the fever subsided.

Figure 2: (a) Anterior surface of the trunk showing the resolution of exanthema with the presence of several slightly hyperpigmented lesions with a scar-like appearance. (b) Posterior surface of the trunk showing the beginning of the resolution of exanthema with the presence of several slightly hyperpigmented lesions with a scar-like appearance.

DISCUSSION

Febrile exanthema, although often benign, may reveal an underlying condition that endangers vital prognosis, thus posing a real challenge for practitioners who must identify patients requiring urgent hospitalization and specialized care.

Drug-induced rashes are, by far, the most frequent causes in adults, followed by viral infections and toxic eruptions [1], with an average incidence estimated at about ten cases per 1,000 new drug users in the U.S. According to a 2012 article by Peter Itin, 45% of patients hospitalized for febrile exanthema had an infectious origin [2].

The clinical presentation of the exanthema itself (rubella-like, scarlet fever-like, measles-like, roseola-like) is not specific and does not suggest a single cause.

Only when the exanthema is accompanied by other associated signs, especially severe ones, should the patient be hospitalized to avoid missing a vital emergency, such as an infectious (often bacterial) or other serious condition. A recent editorial cited a study where over 50% of patients with a febrile state had an undetermined origin [3].

This underscores the importance of thorough history-taking and rigorous clinical examination to target a precise etiology, avoid delaying patient care, and prevent the high costs of unnecessary and non-contributive additional tests. In our patient’s case, the discovery of mild cutaneous-mucosal jaundice, which was not very pronounced, and the observation of general malaise guided us toward a septic origin of the rash associated with acute cholecystitis, after excluding other etiologies and confirming the diagnosis through biological and radiological exams. Thus, the identification of a surgical emergency, especially as it was silent on abdominal examination and the febrile maculopapular exanthema was the only alarming sign, is the uniqueness of our case. This situation was described in 2017, where a febrile maculopapular exanthema was linked to sepsis secondary to pelvic peritonitis and acute cholecystitis [4].

The systemic effects of microorganisms on the skin most often manifest as an exanthema, explaining the pathophysiology of toxic eruptions through two different mechanisms: either due to the direct action of the bacteria or the action of toxins. This explains the cutaneous symptoms in septic states [5].

According to a 2016 study based in Switzerland on cases reported by the Federal Office of Public Health, the most frequently implicated germs in febrile maculopapular exanthema in adults are Meningococcus, toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes responsible for toxic shock syndrome, or germs causing infectious endocarditis [1]. In our patient, E. coli was the germ responsible for toxin secretion due to the presence of acute cholecystitis, which added to the uniqueness of our case [6].

CONCLUSION

Febrile exanthema in adults may be a manifestation of a benign viral infection, yet it should first raise the suspicion of severe etiologies such as drug-induced toxic reactions and bacterial infections that require urgent management. This observation highlights the crucial role of the skin as an alarm signal for septic states, which should prompt the practitioner to uncover underlying conditions that endanger vital prognosis, even in the absence of obvious associated signs. Hence, the importance of thorough history-taking and meticulous clinical examination to guide the diagnosis.

REFERENCES

1.D’incau S, Lebowitz D, Toutous-Trellu L, Eperon G, Huttner B. [Fever and rash in the adult patient]. Rev Med Suisse. 2017;13:798-807.

2.Itin P. Exanthèmes fébriles. Forum Med Suisse. 2013;13:544-47.

3.Horowitz HW. Fever of unknown origin or fever of too many origins?N Engl J Med. 2013;368:197- 9.

4.Fihmi N, Alouani I, Elmrahi A, Zizi N, Dikhaye S. [Approach to the diagnosis of patients with febrile rash]. Pan Afr Med J. 2017;27:227.

5.Martin C, Vincent JL. Sepsis sévère et choc septique. Springer-Verlag France;2005:9.

6.Fuks D, CosséC, Régimbeau J-M. Antibiotic therapy in acute calculous cholecystitis. J Visceral Surg. 2013;150:3-8.