Haemorrhagic monkeypox infection in an immunosuppressed patient with human immunodeficiency virus: beyond the pustules

To the Editor,

A multi-country outbreak of monkeypox infection began in May 2022; the infection has rapidly spread throughout the United States and Western Europe, with >18 000 cases reported from the European countries [1].

Monkeypox is caused by the human Monkeypox virus (MPXV), a double-stranded DNA virus belonging to the family Poxviridae. It is a zoonotic virus that spreads through respiratory droplets, direct contact, or fomites. However, in the ongoing outbreak, the vast majority of cases have been reported in the context of sexual practices, affecting men who have sex with men, with no travel history to the endemic areas [2].

We present the case of a 30-year-old male patient belonging to the men who have sex with men community, who was diagnosed with human immunodeficiency virus (HIV) infection in December 2019. At the time of HIV diagnosis, he refused antiretroviral therapy (ART) and did not return to our practice. He returned in May 2022, when he started co-formulated lamivudine and dolutegravir, following the collection of blood samples and exudates. When he began the ART, he was asymptomatic and had a CD4+ T-cell count of 265 cells/mL (normal value, 404–1612 cells/mL), a CD4+ percentage of 10.20% (normal value, 33–58%), and an HIV viral load of 148.911 copies/mL.

Two weeks later, the patient started feeling unwell, with a fever of up to 39°C, a headache, and dizziness. The rapid influenza and SARS-CoV-2 screening tests were negative. Blood tests showed leukocytosis with white blood cell count of 12.790 cells/μL (normal value, 3.900–10.200 cells/μL), absolute neutrophil count of 8.600 cells/μL (normal value, 1.500–7.700 cells/μL), and a C-reactive protein level of 64.6 mg/L (normal value, <5 mg/L). A positive Chlamydia trachomatis Nucleic Acid Amplification Testing (NAAT) was found in the rectal exudate on review of samples obtained at ART initiation.

The clinical picture was examined as an intercurrent viral infection. Thus, symptomatic treatment with paracetamol and doxycycline for C. trachomatis rectal infection was prescribed.

However, the following day, a nonpruriginous, generalized, maculopapular rash affecting mainly the trunk, buttocks, and upper and lower extremities developed in the patient. The skin examination revealed multiple well-demarcated purpuric macules with central umbilicated pustules and crusts, as shown in Fig. 1 (a) to (d). There were no lesions on the mucous membranes or genital areas. The cervical lymph nodes were palpable.

Fig. 1.

Clinical and histopathological lesions of the patient. (a) Erythemato-purpuric rash, mainly located on the back and buttocks of the patient. (b) Detail of lesions on the left side of the back, showing small central pustules and erosions surrounded by erythemato-purpuric halo. (c) Typical pustular lesion on the wrist. (d) Papular lesion with central umbilication. (e, f) Hematoxylin-eosin staining. Vacuolar interface dermatitis at the purpuric area showing empty vacuoles/bubbles along the basal layer (black triangles) with moderate superficial middle perivascular lymphohistiocytic infiltrate (blue asterisks) and some isolated eosinophils (red arrow). The upper dermis contains prominent telangiectatic vessels (blue arrows).

Although the patient did not meet refer sexual partners in the last 4 weeks or travel abroad (only mentioned a close dance in a nightclub), we assumed a suspected case of monkeypox infection. A viral swab was taken from a deroofed pustule to demonstrate MPXV DNA by a polymerase chain reaction test. Hospital admission was not required. Thereupon, contact isolation at home and symptomatic treatment with paracetamol and a topical antibiotic were suggested. Monkeypox postexposure prophylaxis was not considered in this case because the patient did not declare to have been in close contact with a person testing positive for monkeypox infection.

Given that the purpuric exanthema and temporal sequence could also suggest a drug reaction, we discontinued treatment with doxycycline, and a skin punch-biopsy of a skin lesion on the back was performed.

The PCR test confirmed the presence of MPXV on the skin sample. The biopsy of the purpuric halo depicted an interface pattern with the presence of basal cell vacuolization (hydropic degeneration) and perivascular lymphocytic infiltrate (superficial and middle dermis) with some isolated eosinophils, as shown in Fig. 1(e) and (f). The area corresponding to the central pustule showed signs of folliculitis. Five days later, the patient was asymptomatic, with no new lesions and good recovery from the rash.

We present an atypical case of monkeypox infection in a patient with CDC stage 2 HIV infection (CD4+ T-cell count of 265 cells/mL), who had recently initiated ART. The clinical presentation consisted of an exuberant and generalized purpuric rash. There was no involvement of oral or genital areas, unlike the classic description of monkeypox lesions reported in other cases during the ongoing outbreak in Spain [3]. A hypothesis of this particular case of nongenital involvement could be the ‘close dance contact’ referred to by the patient.

Regarding the atypical haemorrhagic rash, we believe that the fact that the patient's HIV viral load was still unsuppressed in combination with an impaired immune response could have contributed to a more severe disease presentation. These factors may have led to a higher proliferation of the virus in the tissues following infection and, subsequently, to an increasing overflow of viruses into the bloodstream. As MPXV causes a smallpox-like disease in humans, the clinical picture could be interpreted as a mild form of haemorrhagic smallpox-like presentation, similar to the one described in some patients with smallpox and increased viremia 50 years ago. This haemorrhagic variant of smallpox consisted of focal skin eruptions associated with petechial haemorrhages at the base of the vesicles and into the apparently normal skin between focal lesions, as the ones that appeared in our patient [4].

The possibility of immune reconstitution inflammatory syndrome was also assessed, given the recent initiation of ART. However, the patient had neither a CD4+ T-cell count of <200 cells/mL when he started ART nor an AIDS-defining illness (all opportunistic infections were ruled out), and MPXV was not preexisting but a supervening infection. Immune reconstitution inflammatory syndrome (IRIS) was, therefore, dismissed; however, immune restoration was underway. In fact, this newly initiated immune restoration may have generated a diminished response to the new infection, facilitating both transmission with less intense exposure and greater post-infection dissemination with atypical manifestations.

Lastly, a drug reaction was initially suspected, and pathological findings did not completely exclude this option. However, the hazard of a hypersensitivity reaction to doxycycline was highly unlikely because of the complete recovery of the rash within a few days, without corticoid therapy. This clinical course suggests that the exanthema was more likely caused by the viral infection.

To the best of our knowledge, such clinical and pathological presentations of monkeypox have not been previously reported.

The available data suggest that patients with advanced, uncontrolled HIV infection may be at an increased risk of severe or prolonged monkeypox disease following infection [5].

Our patient had not yet achieved viral suppression at the time of monkeypox infection, which may have favoured a more extensive and atypical involvement; however, this condition did not imply the need for hospital admission.

We suggest that monkeypox infection should be closely monitored in immunosuppressed patients and in those initiating ART, as it could trigger a more severe inflammatory response to the virus.

Transparency declaration

The authors declare that they have no conflicts of interest.

Ethics statement

Ethical review and approval were not required for this manuscript by the local legislation and institutional requirements. Written informed consent for the publication of images was obtained from the patient.

Editor: E. Bottieau